Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy

Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy Yuyan Cao, Wei Li, Xiongjun He, Meiqi Liao, Kexin Hu, Shenghao Wu, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4792955/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Anti-HMGCR-positive immune-mediated necrotizing myopathy (IMNM) was initially considered as an exclusively skeletal muscular disease characterized by predominant proximal muscle weakness, observed in elderly patients with an acute duration. However, an increasing number of patients presented extra-muscular involvements coinciding with other autoimmune antibodies. Moreover, some juvenile patients showed chronic weakness of shoulder and hip girdle musculature, resembling limb-girdle muscular dystrophy (LGMD). The present study aims to develop the essential and easily available clinical-pathological classification for anti-HMGCR-positive IMNM patients. Eighteen anti-HMGCR-positive IMNM patients were from Nanfang Hospital and fifty were from published studies. We separated patients into two subgroups, including the overlap (with coexistence of other antibodies) and non-overlap groups (with only anti-HMGCR-positive patients). Medical information, including the clinical and pathological features, together with their treatments and prognosis were compared. We found that compared to the non-overlap anti-HMGCR-positive IMNM group, overlap patients had more extra-muscular symptoms, corresponding to the coexistence of other myositis-specific antibodies (MSAs) and resulting different treatments and prognoses. The early onset age and chronic process, together with the special pathology of resembling LGMD indicated that this is likely a different subtype in non-overlap anti-HMGCR-positive IMNM patients. The results revealed that the anti-HMGCR-positive IMNM patients can be separated into overlap and non-overlap anti-HMGCR-positive IMNM patients. The non-overlap group can be further divided into LGMD-like and non-LGMD-like anti-HMGCR-positive IMNM. However, the confirmed classification of anti-HMGCR-positive IMNM patients requires further proteomics and transcriptomics studies and could potentially be useful for individualized treatment decision making. idiopathic inflammatory myopathy immune-mediated necrotizing myopathy anti-HMGCR myopathy anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibodies Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Idiopathic inflammatory myopathy (IIM), also known as myositis, encompasses a heterogeneous group of autoimmune diseases that involve skeletal muscle and multiple extra-muscular organs such as skin, lungs, joints, and heart [ 1 ]. IIM was initially identified as only polymyositis (PM) and dermatomyositis (DM). However, the classification of IIM has been refined [ 2 , 3 ] and now includes immune-mediated necrotizing myopathy (IMNM), which was distinguished from polymyositis by the European Neuromuscular Centre (ENMC) in 2004. IMNM is characterized by predominant proximal muscle weakness, elevated creatine kinase (CK) levels, and severe myo-fiber necrosis with little or no inflammatory cell infiltration based on muscle biopsy [ 4 ]. Myositis-specific antibodies (MSAs), specifically anti-signal recognition particle (anti-SRP) antibody and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody, are associated with IMNM and in 2017 were included in the diagnostic criteria for IMNM [ 5 – 7 ]. Anti-HMGCR-positive IMNM, also known as anti-HMGCR myopathy, was initially observed in elderly patients with an acute or sub-acute duration, most with statin exposure [ 6 , 8 ]. However, without statin exposure, prevalence was found to be related to geographic region, genetic background, and patient age [ 9 – 13 ]. Anti-HMGCR-positive IMNM was previously considered to be a skeletal muscular disease, exclusive of extra-muscular involvement. Interestingly, more and more cases have been reported with diverse features, especially the patients with coexistence of other MSAs and/or myositis-associated antibodies (MAAs) [ 14 – 16 ]. Moreover, an increasing number of anti-HMGCR-positive IMNM patients with chronic onset have been identified. These patients unexpectedly present with proximally predominant weakness of the shoulder and hip girdle musculature due to muscle fiber dysfunction. These patients have a chronic and slowly progressive disease course, resembling limb-girdle muscular dystrophy, from their early age [ 17 – 22 ]. As a result, LGMD-like pediatric patients were regarded as a special phenotype of anti-HMGCR-positive IMNM [ 18 ]. The different clinical-pathological manifestations of anti-HMGCR-positive IMNM likely provide opportunities for improvement in the precision of disease classification, identification of differing mechanisms of pathogenesis for this rare disease, and the potential development of individualized disease treatments. The various clinical features of anti-HMGCR-positive IMNM patients have all been published previously. However, the reports lacked detailed analysis of a diversity of symptoms, the coexistence of overlap MSAs in these patients, and as such further considerations of clinical and pathologic characteristics are needed. In this study, we retrospectively screened our hospital for anti-HMGCR-positive IMNM patients. These patients, together with previous reported patients were analyzed in order to develop, for the first time, an essential, easily available clinical-pathologic classification of anti-HMGCR-positive IMNM. Methods Patients We retrospectively reviewed anti-HMGCR antibody positive patients from Nanfang Hospital hospitalized between January 2019 and December 2021. We collected clinical features, laboratory finding, and patients’ pathologic manifestations. Similar data from other anti-HMGCR antibody positive patients, reported in previous studies, were included and analyzed as part of the data set [ 14 – 18 ]. Inclusion criteria We enrolled confirmed IIM patients from Nanfang hospital who fulfilled the 2017 ACR/EULAR classification criteria for IIM [ 23 ]. Patients’ blood samples were obtained for the detection of antibodies. The 2018 European Neuromuscular Centre criteria for IMNM were applied to patients with anti-HMGCR antibody [ 7 ]. Patients who had LGMD associated gene or diagnostic mutations of LGMD associated proteins by immunostaining were excluded. Detection of antibodies Detection of MSAs included: anti-EJ, anti-HMGCR, anti-Jo-1, anti-MDA5, anti-Mi-2, anti-NXP2, anti-OJ, anti-PL-7, anti-PL-12, anti-SAE, anti-SRP, and anti-TIF1-γ. Detection of MAAs included: anti-Ku, anti-PM-Scl 75, anti-PM-Scl 100, and anti-Ro52. Analysis was detected by immunoblot (Euroline Myositis Profile 3 Immunoline-blot, Euroimmun, Germany) as previously reported [ 24 ]. Muscle pathology Muscle biopsies were obtained from the quadricep of 15 patients from Nanfang Hospital. Serial 5-µm frozen sections were collected and stained with hematoxylin-eosin, NADH-tetrazolium reductase, modified Gomori’s trichrome, periodic acid-Schiff (PAS), oil red O (ORO), succinate dehydrogenase, and cytochrome C oxidase. Immunohistochemistry staining was performed for: dysferlin, dystrophin, α-sarcoglycans to δ-sarcoglycans, major histocompatibility complex class Ⅰ (MHC-Ⅰ), CD4, CD8, CD68, CD79, and the membrane attack complex (MAC). Muscle biopsies were assessed for the following three aspects; myo-fiber type pathology, muscle tissue pathology, and inflammation. For myo-fiber pathology, the percentage of myo-fibers with atrophy, necrosis, regeneration, heterogeneity (defined as the totality of myo-fibers with atrophy, necrosis, and regeneration) and central nucleus were assessed, by manually counting the total number of myo-fibers. Muscular tissue pathology included the following aspects: perimysial atrophy, endomysial fibrosis, and vasculitis. The characteristics of inflammation were categorized into: 1) the distribution of inflammatory cell as endomysial and/or perimysial; 2) the distribution of MAC deposition as on sarcolemma and/or capillaries; 3) the distribution of MHC-Ⅰ as focal or diffuse. Treatment and prognosis All patients received treatment that included: mono therapy with glucocorticoids (GC), dual therapy with GC and immunosuppressives (IS), as well as triple therapy with GC, IS and intravenous immunoglobulin (IVIg). Response to treatment was recorded as improvement in manual muscle testing (MMT-8) and reduction in CK [ 25 ]. Since there is no consensus definition of IIM remission, the patient’s condition was recorded as disease activity with remission based on changes in CK and MMT-8. Since there is no consensus standard for evaluation of a patient’s prognosis, we defined patients who had remission as (CK reduced to ≤ 500 IU/L and/or MMT-8 score improved ≥ 5) and no relapse as a good prognosis. Patients with disease activity or relapsed after short-time remission were defined as a poor prognosis. Duration of observation was limited to 9 months. Genetic testing Suspected LGMD patients from our hospital received whole exome sequence (WES) testing at Nanfang Hospital. Genomic DNA was extracted from patients’ blood or muscle tissue. Statistical analysis SPSS software (version 24.0; IBM Corp., Armonk, USA) was used for statistical analysis. Qualitative variables were expressed as percentage and absolute frequency, with quantitative variables reported as means ± standard deviation. Comparison of qualitative data was performed by Chi-squared test or Yate’s correction test or Fisher’s exact test. Comparison of quantitative data between two independent samples was performed by Mann-Whitney U test or Student’s t test (two-tailed). Analysis of multiple independent samples was performed by ANOVA or Kruskal-Wallis test. Furthermore, univariable Logistic Regression was used to identify prognosis predictors. Variables with p < 0.1 were included in the multivariable model. Multivariable Logistic Modeling was used to identify independent predictors of prognosis. Overall, p < 0.05 was considered significantly different. Results Clinical features of anti-HMGCR-positive IMNM patients We identified 18 patients diagnosed with anti-HMGCR-positive IMNM. Clinical data are presented in Table 1 . Table 1 Clinical features and pathological manifestations of 18 patients with anti-HMGCR-positive IMNM Gender Onset age (y) Duration (m) Statins exposure Muscular symptoms Extra-muscular symptoms Patient 1 Female 24 4 None Muscle weakness, myalgia None Patient 2 Female 24 2 None Muscle weakness None Patient 3 Female 42 13 None Muscle weakness None Patient 4 Male 54 9 None Muscle weakness None Patient 5 Male 51 132 None Muscle weakness None Patient 6 Female 63 1 Rosuvastatin Muscle weakness None Patient 7 Male 21 14 None Muscle weakness Rash Patient 8 Female 52 11 None Muscle weakness None Patient 9 Male 12 8 None Muscle weakness, myalgia, dysphagia None Patient 10 Female 70 1 None Muscle weakness Arthralgia, cardiac involvement, weight loss Patient 11 Female 73 1 None Dyspnea ILD, weight loss Patient 12 Male 50 72 None Muscle weakness, myalgia Rash Patient 13 Female 43 2 None Muscle weakness, myalgia, dysphagia Arthralgia, rash, ILD, weight loss Patient 14 Female 30 12 None Myalgia Arthralgia Patient 15 Female 37 4 None Muscle weakness, dysphagia None Patient 16 Male 45 10 None Muscle weakness, myalgia Arthralgia, weight loss Patient 17 Female 21 84 None Muscle weakness None Patient 18 Male 19 20 None Muscle weakness None Table 1 continued MMT-8 score before/after therapy Highest CK(IU/L) before/after therapy Anti-HMGCR antibody titer Other MSAs Treatment Prognosis Patient 1 61/63 11914/2856 +++ None GC Poor Patient 2 62/69 7202/1453 +++ None GC, IS, IVIg Good Patient 3 66/70 6865/2735 +++ None GC, IS Poor Patient 4 70/73 3695/2534 +++ None GC, IS, IVIg Poor Patient 5 60/60 1164/195 +++ None GC, IS Poor Patient 6 64/72 4974/3113 +++ None GC, IS, IVIg Good Patient 7 71/76 9708/1594 +++ None GC, IS, IVIg Poor Patient 8 71/77 3759/1105 +++ None GC, IS, IVIg Poor Patient 9 68/75 589/199 + anti-NXP2, anti-Ku, anti-PM/Scl75 GC Good Patient 10 65/73 12555/1880 +++ anti-SRP, anti-SAE1 GC, IS Good Patient 11 80/80 36/15 ++ anti-Ro52, anti-PM/Scl75 GC, IS Good Patient 12 75/80 5215/620 + anti-SRP, anti-OJ, anti-Ro-52, ANA GC, IS Good Patient 13 64/80 589/126 + anti-MDA5, anti-PL7, anti-Ro52 GC, IS Good Patient 14 80/80 862/519 ++ anti-OJ, anti-Ku GC, IS Good Patient 15 58/65 23462/3532 + anti-SRP, anti-Ro-52, ANA GC, IS, IVIg Poor Patient 16 69/74 16037/1320 ++ anti-SRP GC, IS Good Patient 17 49/49 2106/153 +++ None GC, IS, IVIg Poor Patient 18 54/61 21410/5253 ++ None GC, IS Poor ANA anti-nuclear antibody, CK creatine kinase, GC glucocorticoid, IS immunosuppressant, IVIg intravenous immunoglobulin, MMT-8 manual muscle, MSA myositis-specific antibodies Table 1 continued Myofiber type pathology Myofiber type pathology Myofiber type pathology Atrophy Necrosis Regeneration Heterogeneity Central nucleus Features Inflammatory cell Sarcolemma/ Capillary MAC MHC-Ⅰ Patient 1 15% 15% 15% 45% 1% endomysial fibrosis endomysium +/- Focal Patient 2 13% 8% 10% 31% 2% None endomysium +/- Focal Patient 3 10% 9% 3% 22% 1% None None +/- Focal Patient 4 18% 19% 6% 43% 9% None endomysium +/- Focal Patient 5 NA NA NA NA NA NA NA NA NA Patient 6 14% 3% 7% 24% 3% None endomysium +/- Focal Patient 7 8% 2% 5% 15% 22% None endomysium +/- Focal Patient 8 9% 9% 9% 27% 3% None endomysium +/- Focal Patient 9 8% 3% 3% 14% 1% perimysial atrophy perimysium +/ + Diffuse Patient 10 5% 3% 15% 23% 2% None None +/- Focal Patient 11 10% 0% 1% 11% 1% None None +/ + Focal Patient 12 NA NA NA NA NA NA NA NA NA Patient 13 NA NA NA NA NA NA NA NA NA Patient 14 5% 1% 3% 9% 2% vasculitis perimysium, endomysium +/- Focal Patient 15 3% 12% 9% 24% 1% None endomysium +/- Focal Patient 16 2% 10% 12% 24% 1% None perimysium, endomysium +/- Focal Patient 17 16% 6% 7% 29% 22% endomysial fibrosis perimysium, endomysium +/- Focal Patient 18 34% 4% 6% 44% 20% endomysial fibrosis endomysium +/- Focal MAC membrane attack complex, MHC-Ⅰ major histocompatibility complex Ⅰ, NA not available. The age of onset for these patients ranged from 19 to 73 years of age (40.61 ± 18.28 years). Eleven patients (11/18, 61.11%) were female and seven patients (7/18, 38.89%) were male. The median duration from symptom emergence to diagnosis for anti-HMGCR-positive IMNM was 9.50 months (1month-132 months). Seventeen patients (17/18, 94.44%) complained of muscular symptoms, sixteen patients (16/18, 88.89%) had muscle weakness, five patients (5/18, 27.78%) had myalgia, and two patients (2/18, 11.1%) had dyspnea and two patients (2/18, 11.11%) had dysphagia. Seven patients (7/18, 38.9%) had extra-muscular symptoms. Among them, four patients (4/18, 22.22%) had arthralgia and four patients (4/18, 22.22%) had weight loss, three patients (3/18, 16.67%) had a rash, two patients (2/18, 11.11%) had interstitial lung disease (ILD), and one patient (1/18, 5.56%) had cardiac involvement. Nasopharyngeal carcinoma was found in one patient (1/18, 5.56%) during outpatient follow-up. One patient (1/18, 5.56%) had an exposure history to rosuvastatin. All patients were evaluated for muscle strength based on the MMT-8. The score for theMMT-8 ranged from 49 to 80 (65.94 ± 8.17). CK levels were elevated in 17 patients (17/18, 94.44%), while one patient (1/18, 5.56%) remained normal. The serum CK level ranged from 36 to 23462 IU/L (7341.22 ± 7177.24 IU/L). Anti-HMGCR was strongly positive (+++) for ten patients (10/18, 55.56%), moderately positive (++) for four patients (4/18, 22.22%) and weakly positive (+) for four patients (4/18, 22.22%). Anti-HMGCR antibody overlap with other antibodies was observed in eight patients (8/18, 44.44%). The coexistence of anti-HMGCR antibody with one or more MSA and/or MAA was detected in all eight of these patients (8/18, 44.44%), including anti-SAE1 antibody (1/8, 12.50%), anti-MDA5 antibody (1/8, 12.50%), anti-NXP2 antibody (1/8, 12.50%), anti-PL-7 antibody (1/8, 12.50%), anti-Ku antibody (2/8, 25.00%), anti-OJ antibody (2/8, 25.00%), anti-PM-Scl-75 antibody (2/8, 25.00%), anti-Ro-52antibody (4/8, 50.00%), and anti-SRP antibody (4/8, 50.00%). ANA were detected in two patients (2/8, 25.00%). Pathologic manifestations of anti-HMGCR-positive IMNM patients Muscle biopsy results for 15 patients are presented in Table 1 . As for myo-fiber type pathology, the percentage of myo-fibers with atrophy, necrosis, regeneration, heterogeneity, and central nucleus was a range of 2%-34%, 0–19%, 1%-15%, 9–45%, and 1%-22%, respectively. Regarding muscle tissue pathology, three patients (3/15, 20.00%) had endomysial fibrosis, three patients (3/15, 20.00%) had vasculitis, one patient (1/15, 6.67%) had perimysial atrophy. With respect to inflammation, eleven patients (11/15, 73.33%) had endomysial inflammatory cell infiltration, while four patients (4/15, 26.67%) had perimysial inflammatory cell infiltration. Fourteen patients (14/15, 93.33%) had focal distribution of MHC-Ⅰ, while one patient (1/15, 6.67%) had diffuse distribution of MHC-Ⅰ. Sarcolemma MAC deposition was observed in all muscle biopsies (15/15, 100.00%), while capillary MAC positivity was only observed in two patients (2/15, 13.33%). Immunohistochemistry showed that CD4 + T cells, CD8 + T cells, and CD68 + macrophages were the most common inflammatory cells. No diagnostic mutations of known LGMD associated proteins were observed by immunostaining. Treatment and response of anti-HMGCR-positive IMNM patients All 18 patients received treatment (Table 1 ). Nine patients (9/18, 50.00%) were treated with dual-therapy of GC and IS. Seven patients (7/18, 38.89%) received triple-therapy of GC, IS, and IVIg. Two patients (2/18, 11.11%) received mono-therapy with GC. After treatment, myalgia and extra-muscular symptoms disappeared in all patients. All patients had a reduction in CK. Serum CK levels after treatment ranged from 15 to 5253 IU/L (1622.33 ± 1462.54 IU/L), with a reduction range of 31.42%-92.74% (71.29%±18.86%). Except for two patients with normal muscle strength, 14 patients (14/18, 77.8%) had variable muscle strength development, while two patients (2/18, 11.11%) exhibited stabilization. MMT-8 scores after treatment varied from 49 to 80 (70.94 ± 8.50), with an improvement variation of 0–16 (5.00 ± 3.99). Comparison of non-overlap and overlap anti-HMGCR-positive IMNM patients We collected clinical data for 50 patients diagnosed with anti-HMGCR-positive IMNM who had been reported in previous studies as well as 18 patients from our hospital. Since the presence of anti-HMGCR antibody and other antibodies resulted in different clinical features, we separated patients into two subgroups: non-overlap anti-HMGCR-positive IMNM patients and overlap anti-HMGCR-positive IMNM patients. The comparison of clinical data for these two subgroups is presented in Table 2 . Compared to overlap anti-HMGCR-positive IMNM patients, earlier onset age (36.65 ± 18.70 vs 46.14 ± 17.48, p = 0.038) and longer disease duration (56.25 ± 80.58 vs11.53 ± 19.19, p = 0.015) were found in non-overlap patients. Moreover, non-overlap anti-HMGCR patients had a higher frequency of muscle weakness (100.00% vs 75.00%, p = 0.001), but a lower prevalence of myalgia (17.50% vs 46.43%, p = 0.010) and dyspnea (0.00% vs 25.00%, p = 0.001), with lower MMT-8 scores (63.44 ± 7.21 vs 71.77 ± 7.14, p = 0.004) than overlap patients. With regard to extra-muscular symptoms, overlap anti-HMGCR-positive IMNM patients had a higher prevalence of extra-muscular symptoms (89.29% vs 17.50%, p < 0.0001), including ILD (28.57% vs 2.50%, p = 0.003), arthralgia (32.10% vs 0.00%, p = 0.0001), weight (25.00% vs 2.50%, p = 0.014), and skin involvement (53.57% vs 15.00%, p = 0.001) than non-overlap patients. Overlap anti-HMGCR-positive IMNM patients had a lower frequency of treatment with IVIg (9.50% vs 60.00%, p = 0.001) than non-overlap patients. Correlations between overlap antibodies and muscular and extra-muscular symptoms in overlap anti-HMGCR-positive IMNM patients are shown in Fig. 1 . With regard to muscular symptoms, limb muscle weakness was predominantly presented in patients except for patients with anti-MDA5 antibody, all of which (5/5, 100.0%) complained of dyspnea, and patients with anti-PM-Scl-75 antibody presenting with dysphagia (2/3, 66.67%). Myalgia was shown in all patients with anti-Ku antibody (3/3, 100.00%) and anti-OJ antibody (2/2, 100.00%). As for extra-muscular symptoms, all patients with anti-MDA5 antibody (5/5, 100.00%) showed skin involvement and ILD. Most patients with anti-Jo-1 antibody (2/3, 66.67%) presented with ILD and arthralgia. Table 2 Comparison of clinical features between non-overlap and overlap patients Non-overlap (n = 40) Overlap (n = 28) p Clinical data Female 23/36 (63.89) 16 (57.14) 0.583 Onset age (years old) 36.65 ± 18.70 46.14 ± 17.48 0.038 * Duration (months) 56.25 ± 80.58 11.53 ± 19.19 0.015 MMT-8 63.44 ± 7.21 71.77 ± 7.14 0.004 * Highest CK (IU/L) 7401.54 ± 5616.61 8470.60 ± 7289.30 0.609 Clinical symptoms Muscular symptoms 40 (100.00) 28 (100.00) 1.000 Muscle weakness 40 (100.00) 21 (75.00) 0.001 * Myalgia 7 (17.50) 13 (46.43) 0.010 * Dyspnea 0 (0.00) 7 (25.00) 0.001 * Dysphagia 5 (12.50) 8 (28.57) 0.097 Extra-muscular symptoms 7 (17.50) 25 (89.29) < 0.0001 * ILD 1 (2.50) 8 (28.57) 0.003 * Arthralgia 0 (0.00) 9 (32.14) 0.0001 * Loss of weight 1 (2.50) 7 (25.00) 0.014 * Skin involvement 6 (15.00) 15 (53.57) 0.001 * Treatment and outcomes With IVIg 21/35 (60.00) 2/21 (9.50) 0.001 * Good prognosis 2/10 (20.00) 7/8 (87.50) 0.015 * CK creatine kinase, ILD interstitial lung disease, IVIg intravenous immunoglobulin, MMT-8 manual muscle testing. * P < 0.05. The muscular and extra-muscular symptoms in all overlap anti-HMGCR-positive IMNM patients. The heatmap showed the percentage of muscular and extra-muscular symptoms in patients with different overlap antibodies. With regard to muscular symptoms, limb muscle weakness was predominantly presented in patients except for patients Anti-MDA5 antibody complaining of with dyspnea (5/5, 100.00%) and anti-PM-Scl-75 antibody of dysphagia (2/3, 66.67%). Myalgia was shown in all patients with anti-Ku antibody (3/3, 100.00%) and anti-OJ antibody (2/2, 100.00%). As for extra-muscular symptoms, all patients with anti-MDA5 antibody (5/5, 100.00%) showed skin involvement and ILD. Most patients with anti-Jo-1 antibody (2/3, 66.67%) presented with ILD and arthralgia. Comparison of the 15 biopsies from non-overlap and overlap anti-HMGCR-positive IMNM patients from our hospital is shown (Fig. 2 ). As for myo-fiber type pathology, non-overlap anti-HMGCR-positive IMNM patients had a higher percentage of myo-fibers with atrophy (15.22%±7.79% vs 5.50%±3.02%, p = 0.013), central nucleus (9.22%±9.40% vs 1.33%±0.52%, p = 0.028) and heterogeneity (31.11%±10.69% vs 17.50%±6.95%, p = 0.017) compared to overlap patients. No statistically significant difference was observed in myo-fibers with necrosis (8.33%±5.61% vs 4.83%±4.96%, p = 0.238) and regeneration (7.56%±3.47% vs 7.17%±5.67%, p = 0.871). For muscle tissue pathology, we found no significant difference in the prevalence of perimysial atrophy (0.00% vs 16.67%, p = 0.400), endomysial fibrosis (33.33% vs 0.00%, p = 0.229), or vasculitis (11.11% vs 16.67%, p = 1.000) between overlap and non-overlap anti-HMGCR-positive IMNM patients. With regard to inflammatory pathology, there was no difference in endomysial inflammatory cell infiltration (88.89% vs 50.00%, p = 0.235), perimysial inflammatory cells infiltration (11.11% vs 50.00%, p = 0.235), the focal distribution of MHC-Ⅰ (100.00% vs 83.33%, p = 0.400), sarcolemma MAC deposit (100.00% vs 100.00%, p = 1.000), or capillary MAC deposit (0.00% vs 33.33%, p = 0.143) between non-overlap and overlap anti-HMGCR-positive IMNM patients. Comparison of non-overlap and overlap anti-HMGCR-positive IMNM patient pathologic manifestations. For myo-fiber pathology, non-overlap anti-HMGCR-positive IMNM presented with a higher percentage of myo-fibers with atrophy (15.22%±7.79% vs 5.50%±3.02%, p = 0.013), central nucleus (9.22%±9.40% vs 1.33%±0.52%, p = 0.028) and heterogeneity (31.11%±10.69% vs 17.50%±6.95%, p = 0.017) compared to overlap patients. For muscle tissue pathology and inflammatory pathology, there were no significant differences. Differences in treatment between non-overlap and overlap anti-HMGCR-positive IMNM patients are shown in Table 2 . Non-overlap anti-HMGCR-positive IMNM patients had a higher frequency of IVIg use than overlap patients (60.00% vs 9.50%, p = 0.001). Response to the treatment is presented in Fig. 3 A, B. Compared with non-overlap anti-HMGCR-positive IMNM patients, overlap patients had greater improvement (8.00 ± 4.10 vs 4.20 ± 2.90, p = 0.047) in MMT-8 scores after treatment. However, there was no significant difference in the percentage of CK reduction (69.05%±20.22% vs 74.10%±17.94%, p = 0.588) between non-overlap and overlap anti-HMGCR-positive IMNM patients. Additionally, overlap anti-HMGCR-positive IMNM patients had a higher prevalence of a good prognosis than non-overlap patients (87.50% vs 20.00%, p = 0.015) (Table 2 ). A comparison of patients with a good and a poor prognosis was performed. Anti-HMGCR-positive IMNM patients who had a good prognosis had higher MMT-8 scores compared to patients who had a poor prognosis (69.67 ± 6.98 vs 62.22 ± 7.87, p = 0.050) ( Suppl. Table 1 ). By univariable analysis, overlap antibody (B = 28.0, p = 0.012) was found to be a good prognostic predictor, while MMT-8 score was not (B = 1.2, p = 0.079). By multivariable analysis, overlap antibody (B = 28.0, p = 0.012) was identified as an independent predictor of a good prognosis ( Suppl. Table 2 ). ROC analysis demonstrated a good performance for overlap antibody as a predictor of prognosis, with an AUC of 0.833 ( p = 0.017, 95%CI, 0.629-1.000) (Fig. 3 C). A cut-off value (1.50) had a sensitivity of 77.8% and specificity of 88.9%. Treatment response and prognosis for non-overlap and overlap anti-HMGCR-positive IMNM patients. ( A ) Percentage of CK reduction: there was no significant difference between non-overlap and overlap patients. ( B ) MMT-8 improvement: overlap patients had greater improvement in MMT-8 scores after treatment (8.00 ± 4.10 vs 4.20 ± 2.90, p = 0.047) than non-overlap patients. ( C ) The area under curve (AUC) values indicate that overlap antibody can serve as a predictor of a good prognosis, with an AUC of 0.833 ( p = 0.017, 95%CI, 0.629-1.000). A cut-off value (1.50) had a sensitivity of 77.8% and specificity of 88.9%. Error bar = Standard deviation. * p < 0.05. Comparison of non-LGMD-like and LGMD-like anti-HMGCR-positive IMNM patients Among the patients diagnosed with non-overlap anti-HMGCR-positive IMNM, a special type of disease resembling LGMD has been identified that does not have an associated pathogenic gene. To demonstrate whether the LGMD-like anti-HMGCR-positive IMNM is a unique subtype of non-overlap anti-HMGCR-positive IMNM, we separated non-overlap anti-HMGCR-positive IMNM patients into two phenotypes: non-LGMD-like anti-HMNGCR-positive IMNM and LGMD-like anti-HMNGCR-positive IMNM. Comparisons were made of the clinical-pathologic characteristics of the two phenotypes (Table 3 ). With regard to clinical characteristics, LGMD-like anti-HMGCR-positive IMNM patients had an earlier age of onset (21.33 ± 14.13 vs 44.68 ± 16.94, p < 0.0001), longer duration (128.75 ± 97.92 vs 15.90 ± 28.80, p < 0.0001), and lower MMT-8 scores (51.50 ± 3.54 vs 68.33 ± 7.21 p = 0.003) than non-LGMD-like patients. With regard to myo-fiber type pathology, LGMD-like anti-HMGCR-positive patients exhibited profound myo-fibers with atrophy and predominant myo-fibers with the central nucleus, resembling muscular dystrophy more than the shared characteristics of severe myo-fiber necrosis and regeneration (Fig. 4 ). There was no remarkable difference with regard to muscle tissue or inflammatory pathology. With regard to different types of CD staining for T lymphocytic cell, there were also no significant differences. Table 3 Comparison of clinical features between non-LGMD-like and LGMD-like patients Non-LGMD-like (n = 28) LGMD-like (n = 12) p Clinical data Female 18 (64.29) 4/8 (50.00) 0.683 Onset age (years old) 44.68 ± 16.94 21.33 ± 14.13 < 0.0001 * Duration (months) 15.90 ± 28.80 128.75 ± 97.92 < 0.0001 * MMT-8 68.33 ± 7.21 51.50 ± 3.54 0.003 * Highest CK (IU/L) 7160.65 ± 5629.42 10339.50 ± 8150.56 0.203 Clinical symptoms Muscular symptoms 28 (100.00) 12 (100.00) 1.000 Muscle weakness 28 (100.00) 12 (100.00) 1.000 Myalgia 7 (25.00) 0 (0.00) 0.081 Dyspnea 0 (0.00) 0 (0.00) 1.000 Dysphagia 4 (14.29) 1 (8.33) 1.000 Extra-muscular symptoms 6 (21.43) 1 (8.33) 0.586 ILD 1 (3.57) 0 (0.00) 1.000 Arthralgia 0 (0.00) 0 (0.00) 1.000 Loss of weight 1 (3.57) 0 (0.00) 1.000 Skin involvement 5 (17.88) 1 (8.33) 0.772 Treatment With IVIg 11/23 (47.83) 7/8 (87.50) 0.095 CK creatine kinase, ILD interstitial lung disease, IVIg intravenous immunoglobulin, MMT-8 manual muscle testing. * P < 0.05. Pathological manifestations of LGMD-like ( A - C ) and non-LGMD-like anti-HMGCR-positive IMNM patients ( D - F ). LGMD-like patient’s biopsy showed profound myo-fibers with atrophy (black arrowhead) and central nucleus (black arrow) ( A ) and focal CD4 (black arrow) ( B ) and CD68 lymphocytic infiltration (black arrow) ( C ). Non-LGMD-like patient’s biopsy showed predominant myo-fibers with necrosis and regeneration (white arrow) ( D ) and scattered CD4 lymphocytic infiltration (black arrow) ( E ) and focal CD68 lymphocytic infiltration (black arrow) ( F ). Scale bar = 100 µm. Discussion In this study, we collected clinical and pathologic data from anti-HMGCR-positive IMNM patients in our hospital and similar patient data from previous studies. In this manner we developed an essential and easily available clinical-pathological classification of anti-HMGCR-positive IMNM. Anti-HMGCR antibody was previously considered distinguishable in that they are mutually exclusive in patients [ 26 – 28 ], but a growing number of anti-HMGCR-IMNM patients with the coexistence of other MSAs has been reported, with unusual symptoms [ 14 – 16 ]. Likewise, nearly half anti-HMGCR-positive IMNM patients admitted to our hospital had antibodies other than anti-HMGCR antibody, exhibiting distinguishable symptoms. Therefore, we evaluated the coexistence of anti-HMGCR antibody and other antibodies appears to be associated with unique clinical and pathological features, suggesting the possibility of a universal phenomenon. Different from the conventional symptoms of non-overlap anti-HMGCR-positive IMNM, in our study, the overlap anti-HMGCR-positive IMNM was found to more resemble dermatomyositis, presenting with muscle weakness and extra-muscular symptoms, while extra-muscular symptoms in overlap patients mostly corresponded to MSAs other than anti-HMGCR antibody. Similar to the previous studies, overlap anti-HMGCR-positive IMNM patients with anti-ARS antibodies generally showed anti-synthetase syndrome [ 15 , 16 ], while patients with anti-MDA antibody commonly presented as skin involvement and ILD [ 14 ]. Despite the striking similarity to DM clinical symptoms, nearly all muscle biopsies of patients with overlap anti-HMGCR-positive IMNM conformed to the manifestation of IMNM [ 14 – 16 ]. As a result, overlap anti-HMGCR-positive IMNM is probably a special sub-type of anti-HMGCR-positive IMNM, presenting with both dermatomyositis-like clinical features and pathological manifestations, indicating immune-mediated necrotizing myopathy. Consequently, we hypothesize that for overlap anti-HMGCR-positive IMNM patients, anti-HMGCR antibody plays a dominant role in muscle injury, while other antibodies associate with extra-muscular symptoms. Interestingly, few overlap patients complained of dyspnea or dysphagia, without limb muscle weakness, especially in patients with anti-MDA5 patients [ 14 , 16 ]. Moreover, higher MMT-8 score or nearly normal muscle strength in overlap anti-HMGCR-positive IMNM patients can be explained by a lower percentage of myo-fibers with atrophy and heterogeneity, because of reduced muscle injury. The likely reason is that anti-HMGCR is not the important antibody when other MSAs are present. Therapy and treatment responses were compared for overlap and non-overlap anti-HMGCR-positive IMNM patients. Nearly all patients with overlap anti-HMGCR IMNM received dual therapy with GC and IS, while half of non-overlap patients required triple therapy of GC, IS, and IVIg, which prevented worsening symptoms. Post-treatment MMT-8 score improvement was significantly higher in overlap anti-HMGCR IMNM patients, indicating that overlap patients may respond well to dual therapy, while non-overlap anti-HMGCR-positive IMNM patients may have a relatively limited response to such treatment. In terms of prognosis, overlap anti-HMGCR-positive IMNM patients tend to have a good prognosis compared to non-overlap patients. This may be explained by weakly or moderately positive anti-HMGCR antibody existing in most overlap patients. As such, differing clinical-pathological features suggest that the mechanism of pathogenesis of it is probably different, but such an assertion requires further investigation. LGMD-like anti-HMGCR-positive IMNM patients (who always have only anti-HMGCR antibody) are typically children and teenagers with a chronic and progressive disease course [ 17 – 22 ]. In addition to negative family history and negative genetic testing results, none of the patients diagnosed with LGMD-like anti-HMGCR-positive IMNM complained of myalgia, although a few patients exhibited extra-muscular symptoms. Consistent with the published literature, pathological manifestations of this subtype were distinguished by considerable atrophic myo-fibers and predominant myo-fibers with central nucleus [ 17 , 18 ]. However, confirmation of these results requires assessment of more LGMD-like anti-HMGCR-positive IMNM patients. Myo-fiber heterogeneity, together with endomysial fibrosis found in the LGMD-like subtype, can likely be explained by the chronicity of the process. Considering the peculiar clinical and special pathological manifestations, we speculate a distinctive pathogenesis for LGMD-like anti-HMGCR-positive IMNM patients with the possibility of genetic factor involvement. There are limitations to this study. First, this study is retrospective for anti-HMGCR-positive IMNM patients, so information bias is inevitable. Second, a limited number of anti-HMGCR-positive IMNM patients, especially LGMD-like anti-HMGCR-positive IMNM patients were constraint for this study. Finally, proteomics, transcriptomics, and metabolomics analysis is essential for a more complete evaluation of the involved mechanisms of pathogenesis. Conclusion In conclusion, we separated overlap anti-HMGCR-positive IMNM patients from non-overlap anti-HMGCR-positive IMNM patients based on the antibodies involved in extra-muscular symptoms and clinical and pathological characteristics. Differences among LGMD-like anti-HMGCR-positive IMNM patients indicated the probability that different subtypes exist within non-overlap anti-HMGCR-positive IMNM patients. However, classification confirmation of anti-HMGCR-positive IMNM patients requires further proteomics, transcriptomics and metabolomics analysis. Such analysis has the potential to provide individualized patient treatment. Declarations Conflict of interest The authors declare no conflict of interest. Ethics approval This study involves human participants and the study was approved by the Ethics Committee of Nanfang Hospital, Southern Medical University, Guangzhou 510515, China (No. NFEC-2023-130). The study followed the principles of the Declaration of Helsinki. Consent to participate As the data were anonymized and collected retrospectively, no informed consent from participants was required in accordance with the ethics committee. Consent to publish Not applicable. Funding The authors declare that no funds, grants, or other support were received during the preparation of this manuscript. Author Contribution Study conception and design: HZ and QH. Acquisition of data: WL, YC and XH. Analysis and interpretation of data: WL, YC and XH. Writing of the manuscript: all authors. Critical revision of the manuscript for important intellectual content: all authors. All authors had access to the data, commented on the report drafts and approved the final submitted version. Acknowledgements We would like to thank the patients, and study nurses who participated in this study Data availability The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. References Tanboon J, Nishino I. Classification of idiopathic inflammatory myopathies: pathology perspectives. Curr Opin Neurol. 2019;32(5):704–14. 10.1097/WCO.0000000000000740 . Luo YB, Mastaglia FL. Dermatomyositis, polymyositis and immune-mediated necrotising myopathies. Biochim Biophys Acta. 2015;1852(4):622–32. 10.1016/j.bbadis.2014.05.034 . Sasaki H, Kohsaka H. Current diagnosis and treatment of polymyositis and dermatomyositis. Mod Rheumatol. 2018;28(6):913–21. 10.1080/14397595.2018.1467257 . Hoogendijk JE, Amato AA, Lecky BR et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10–12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004;14(5):337–345. 10.1016/j.nmd.2004.02.006 Christopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62(9):2757–66. 10.1002/art.27572 . Mammen AL, Chung T, Christopher-Stine L, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63(3):713–21. 10.1002/art.30156 . Allenbach Y, Mammen AL, Benveniste O, Stenzel W, Immune-Mediated Necrotizing Myopathies Working Group. 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14–16 October 2016. Neuromuscul Disord. 2018;28(1):87–99. 10.1016/j.nmd.2017.09.016 Barrons R. Statin-Associated Autoimmune Myopathy: Review of the Literature. J Pharm Pract. 2023;36(2):383–93. 10.1177/08971900211040291 . Prieto-Peña D, Ocejo-Vinyals JG, Mazariegos-Cano J, et al. Epidemiological and genetic features of anti-3–hydroxy-3-methylglutaryl-CoA reductase necrotizing myopathy: Single-center experience and literature review. Eur J Intern Med. 2022;101:86–92. 10.1016/j.ejim.2022.04.017 . Ge Y, Lu X, Peng Q, Shu X, Wang G. Clinical Characteristics of Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Antibodies in Chinese Patients with Idiopathic Inflammatory Myopathies. PLoS ONE. 2015;10(10):e0141616. 10.1371/journal.pone.0141616 . Published 2015 Oct 28. Watanabe Y, Suzuki S, Nishimura H, et al. Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Med (Baltim). 2015;94(4):e416. 10.1097/MD.0000000000000416 . Limaye V, Bundell C, Hollingsworth P, et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve. 2015;52(2):196–203. 10.1002/mus.24541 . Tiniakou E, Pinal-Fernandez I, Lloyd TE, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017;56(5):787–94. 10.1093/rheumatology/kew470 . Huang L, Wang L, Yang Y, et al. Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis. Med (Baltim). 2018;97(47):e13236. 10.1097/MD.0000000000013236 . Jiao Y, Cai S, Lin J, et al. Statin-naïve anti-HMGCR antibody-mediated necrotizing myopathy in China. J Clin Neurosci. 2018;57:13–9. 10.1016/j.jocn.2018.08.010 . Szczesny P, Barsotti S, Nennesmo I, Danielsson O, Dastmalchi M. Screening for Anti-HMGCR Antibodies in a Large Single Myositis Center Reveals Infrequent Exposure to Statins and Diversiform Presentation of the Disease. Front Immunol. 2022;13:866701. 10.3389/fimmu.2022.866701 . Published 2022 May 4. Liang WC, Uruha A, Suzuki S, et al. Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxford). 2017;56(2):287–93. 10.1093/rheumatology/kew386 . Mohassel P, Landon-Cardinal O, Foley AR, et al. Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. Neurol Neuroimmunol Neuroinflamm. 2018;6(1):e523. 10.1212/NXI.0000000000000523 . Published 2018 Dec 12. Allenbach Y, Drouot L, Rigolet A, et al. Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Med (Baltim). 2014;93(3):150–7. 10.1097/MD.0000000000000028 . Kishi T, Rider LG, Pak K, et al. Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients. Arthritis Care Res (Hoboken). 2017;69(7):1088–94. 10.1002/acr.23113 . Velardo D, Faravelli I, Cinnante C, Moggio M, Comi GP. Pediatric anti-HMGCR necrotizing myopathy: diagnostic challenges and literature review. Neurol Sci. 2020;41(10):3009–13. 10.1007/s10072-020-04491-6 . Tansley SL, Betteridge ZE, Simou S et al. Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients [published correction appears in J Rheumatol. 2017;44(9):1417]. J Rheumatol. 2017;44(4):488–492. 10.3899/jrheum.160871 Lundberg IE, Tjärnlund A, Bottai M et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups [published correction appears in Ann Rheum Dis. 2018;77(9):e64]. Ann Rheum Dis. 2017;76(12):1955–1964. 10.1136/annrheumdis-2017-211468 Yang H, Tian X, Zhang L, et al. Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort. BMC Musculoskelet Disord. 2022;23(1):425. 10.1186/s12891-022-05372-z . Published 2022 May 6. Rider LG, Koziol D, Giannini EH, et al. Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies. Arthritis Care Res (Hoboken). 2010;62(4):465–72. 10.1002/acr.20035 . Ghirardello A, Gatto M, Franco C, et al. Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies. Diagnostics (Basel). 2023;13(19):3080. Published 2023 Sep 28. Alenzi FM. Myositis Specific Autoantibodies: A Clinical Perspective. Open Access Rheumatol. 2020;12:9–14. 10.2147/OARRR.S231195 . Published 2020 Jan 14. Satoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EK. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy. Clin Rev Allergy Immunol. 2017;52(1):1–19. 10.1007/s12016-015-8510-y . Hamaguchi Y, Fujimoto M, Matsushita T, et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS ONE. 2013;8(4):e60442. 10.1371/journal.pone.0060442 . Additional Declarations No competing interests reported. Supplementary Files SupplementaryMaterialTable1.docx SupplementaryMaterialTable2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4792955","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":343273396,"identity":"9042ad0a-af0c-4b9e-a16a-d689ba140259","order_by":0,"name":"Yuyan Cao","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yuyan","middleName":"","lastName":"Cao","suffix":""},{"id":343273397,"identity":"be43953b-a755-4623-a8ed-1613dd919eb4","order_by":1,"name":"Wei Li","email":"","orcid":"","institution":"Nanfang Hospital, Southern Medical 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Zheng","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/0lEQVRIiWNgGAWjYDACCSBmbGDgsW9mbHzwASJmQJwWA3bmw4YzSNHCYMDPlibMQ4wW+dnNxx5+3XFYxpyZx4zZ5s+2xAb25m0SDDV3cGphnHMs3Vj2zGEey2Yes8e5bbcTG3iOlUkwHHuGUwuzRI6ZtGTbYR6GwzzmxrkNQC1AEQnGhsM4tbBJ5H+DaTGTtvgD1CL/Br8WHokcNsmPQC0Gh9nSpBnYQLbw4NciIZFmJs3Yls4j2QwM5N6228ZtPGnFFgnHcGuRn5H8TPJnm7U9P//Bxgc//tyW7Wc/vPHGhxrcWsBBwIPiOxCRgFcDMKB/EFAwCkbBKBgFIxwAAIJDUZNt+ApFAAAAAElFTkSuQmCC","orcid":"","institution":"Nanfang Hospital, Southern Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hui","middleName":"","lastName":"Zheng","suffix":""}],"badges":[],"createdAt":"2024-07-24 06:48:47","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4792955/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4792955/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":63420158,"identity":"68b1efb3-a2c8-45d7-8c91-720cc43d481d","added_by":"auto","created_at":"2024-08-28 02:35:53","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":990744,"visible":true,"origin":"","legend":"\u003cp\u003eThe muscular and extra-muscular symptoms in all overlap anti-HMGCR-positive IMNM patients. The heatmap showed the percentage of muscular and extra-muscular symptoms in patients with different overlap antibodies. With regard to muscular symptoms, limb muscle weakness was predominantly presented in patients except for patients Anti-MDA5 antibody complaining of with dyspnea (5/5, 100.00%) and anti-PM-Scl-75 antibody of dysphagia (2/3, 66.67%). Myalgia was shown in all patients with anti-Ku antibody (3/3, 100.00%) and anti-OJ antibody (2/2, 100.00%). As for extra-muscular symptoms, all patients with anti-MDA5 antibody (5/5, 100.00%) showed skin involvement and ILD. Most patients with anti-Jo-1 antibody (2/3, 66.67%) presented with ILD and arthralgia.\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/6755c000a81165b115a3809e.png"},{"id":63420162,"identity":"41d11b70-8302-4fae-b758-90952df619f2","added_by":"auto","created_at":"2024-08-28 02:35:53","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1907269,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of non-overlap and overlap anti-HMGCR-positive IMNM patient pathologic manifestations. For myo-fiber pathology, non-overlap anti-HMGCR-positive IMNM presented with a higher percentage of myo-fibers with atrophy (15.22%±7.79% vs 5.50%±3.02%, \u003cem\u003ep\u003c/em\u003e=0.013), central nucleus (9.22%±9.40% vs 1.33%±0.52%, \u003cem\u003ep\u003c/em\u003e=0.028) and heterogeneity (31.11%±10.69% vs 17.50%±6.95%, \u003cem\u003ep\u003c/em\u003e=0.017) compared to overlap patients. For muscle tissue pathology and inflammatory pathology, there were no significant differences.\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/408e11ca84616f67793f31c8.png"},{"id":63420160,"identity":"1f7e4331-a40b-4126-abeb-9721dd30b248","added_by":"auto","created_at":"2024-08-28 02:35:53","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1550886,"visible":true,"origin":"","legend":"\u003cp\u003eTreatment response and prognosis for non-overlap and overlap anti-HMGCR-positive IMNM patients. (\u003cstrong\u003eA\u003c/strong\u003e) Percentage of CK reduction: there was no significant difference between non-overlap and overlap patients. (\u003cstrong\u003eB\u003c/strong\u003e) MMT-8 improvement: overlap patients had greater improvement in MMT-8 scores after treatment (8.00±4.10 vs 4.20±2.90, \u003cem\u003ep\u003c/em\u003e=0.047) than non-overlap patients. (\u003cstrong\u003eC\u003c/strong\u003e) The area under curve (AUC) values indicate that overlap antibody can serve as a predictor of a good prognosis, with an AUC of 0.833 (\u003cem\u003ep\u003c/em\u003e=0.017, 95%CI, 0.629-1.000). A cut-off value (1.50) had a sensitivity of 77.8% and specificity of 88.9%. Error bar= Standard deviation. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003ep \u003c/em\u003e\u0026lt;0.05.\u003c/p\u003e","description":"","filename":"Fig.3.png","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/f0feb9af2987fc23c6b0e7bc.png"},{"id":63420159,"identity":"71fb7cef-70ed-4652-8411-e411717da168","added_by":"auto","created_at":"2024-08-28 02:35:53","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":6707414,"visible":true,"origin":"","legend":"\u003cp\u003ePathological manifestations of LGMD-like (\u003cstrong\u003eA\u003c/strong\u003e-\u003cstrong\u003eC\u003c/strong\u003e) and non-LGMD-like anti-HMGCR-positive IMNM patients (\u003cstrong\u003eD\u003c/strong\u003e-\u003cstrong\u003eF\u003c/strong\u003e). LGMD-like patient’s biopsy showed profound myo-fibers with atrophy (black arrowhead) and central nucleus (black arrow) (\u003cstrong\u003eA\u003c/strong\u003e) and focal CD4 (black arrow) (\u003cstrong\u003eB\u003c/strong\u003e) and CD68 lymphocytic infiltration (black arrow) (\u003cstrong\u003eC\u003c/strong\u003e). Non-LGMD-like patient’s biopsy showed predominant myo-fibers with necrosis and regeneration (white arrow) (\u003cstrong\u003eD\u003c/strong\u003e) and scattered CD4 lymphocytic infiltration (black arrow) (\u003cstrong\u003eE\u003c/strong\u003e) and focal CD68 lymphocytic infiltration (black arrow) (\u003cstrong\u003eF\u003c/strong\u003e). Scale bar= 100 μm.\u003c/p\u003e","description":"","filename":"Fig.4.png","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/1d5120a14a134d89d81affdb.png"},{"id":69376292,"identity":"6b526a59-3234-4fd8-970b-051c4174bd60","added_by":"auto","created_at":"2024-11-19 17:17:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":21343114,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/0d6c86ef-9abb-4a6a-b06c-6ce4af95247d.pdf"},{"id":63420163,"identity":"fa2f4abd-0164-4658-9cec-b66b9db6c7fd","added_by":"auto","created_at":"2024-08-28 02:35:53","extension":"docx","order_by":9,"title":"","display":"","copyAsset":false,"role":"supplement","size":17666,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialTable1.docx","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/4418534c5b7140e6a12a6f18.docx"},{"id":63421070,"identity":"2d2e7da9-0b57-4d5f-b113-609f35f51bc0","added_by":"auto","created_at":"2024-08-28 02:43:53","extension":"docx","order_by":10,"title":"","display":"","copyAsset":false,"role":"supplement","size":15960,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryMaterialTable2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4792955/v1/9d029927b7cfe70206362bb2.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy","fulltext":[{"header":"Background","content":"\u003cp\u003eIdiopathic inflammatory myopathy (IIM), also known as myositis, encompasses a heterogeneous group of autoimmune diseases that involve skeletal muscle and multiple extra-muscular organs such as skin, lungs, joints, and heart [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIIM was initially identified as only polymyositis (PM) and dermatomyositis (DM). However, the classification of IIM has been refined [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] and now includes immune-mediated necrotizing myopathy (IMNM), which was distinguished from polymyositis by the European Neuromuscular Centre (ENMC) in 2004. IMNM is characterized by predominant proximal muscle weakness, elevated creatine kinase (CK) levels, and severe myo-fiber necrosis with little or no inflammatory cell infiltration based on muscle biopsy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Myositis-specific antibodies (MSAs), specifically anti-signal recognition particle (anti-SRP) antibody and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibody, are associated with IMNM and in 2017 were included in the diagnostic criteria for IMNM [\u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eAnti-HMGCR-positive IMNM, also known as anti-HMGCR myopathy, was initially observed in elderly patients with an acute or sub-acute duration, most with statin exposure [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, without statin exposure, prevalence was found to be related to geographic region, genetic background, and patient age [\u003cspan additionalcitationids=\"CR10 CR11 CR12\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Anti-HMGCR-positive IMNM was previously considered to be a skeletal muscular disease, exclusive of extra-muscular involvement. Interestingly, more and more cases have been reported with diverse features, especially the patients with coexistence of other MSAs and/or myositis-associated antibodies (MAAs) [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, an increasing number of anti-HMGCR-positive IMNM patients with chronic onset have been identified. These patients unexpectedly present with proximally predominant weakness of the shoulder and hip girdle musculature due to muscle fiber dysfunction. These patients have a chronic and slowly progressive disease course, resembling limb-girdle muscular dystrophy, from their early age [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. As a result, LGMD-like pediatric patients were regarded as a special phenotype of anti-HMGCR-positive IMNM [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. The different clinical-pathological manifestations of anti-HMGCR-positive IMNM likely provide opportunities for improvement in the precision of disease classification, identification of differing mechanisms of pathogenesis for this rare disease, and the potential development of individualized disease treatments.\u003c/p\u003e \u003cp\u003eThe various clinical features of anti-HMGCR-positive IMNM patients have all been published previously. However, the reports lacked detailed analysis of a diversity of symptoms, the coexistence of overlap MSAs in these patients, and as such further considerations of clinical and pathologic characteristics are needed.\u003c/p\u003e \u003cp\u003eIn this study, we retrospectively screened our hospital for anti-HMGCR-positive IMNM patients. These patients, together with previous reported patients were analyzed in order to develop, for the first time, an essential, easily available clinical-pathologic classification of anti-HMGCR-positive IMNM.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePatients\u003c/h2\u003e \u003cp\u003eWe retrospectively reviewed anti-HMGCR antibody positive patients from Nanfang Hospital hospitalized between January 2019 and December 2021. We collected clinical features, laboratory finding, and patients\u0026rsquo; pathologic manifestations. Similar data from other anti-HMGCR antibody positive patients, reported in previous studies, were included and analyzed as part of the data set [\u003cspan additionalcitationids=\"CR15 CR16 CR17\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eInclusion criteria\u003c/h2\u003e \u003cp\u003eWe enrolled confirmed IIM patients from Nanfang hospital who fulfilled the 2017 ACR/EULAR classification criteria for IIM [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Patients\u0026rsquo; blood samples were obtained for the detection of antibodies. The 2018 European Neuromuscular Centre criteria for IMNM were applied to patients with anti-HMGCR antibody [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Patients who had LGMD associated gene or diagnostic mutations of LGMD associated proteins by immunostaining were excluded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eDetection of antibodies\u003c/h2\u003e \u003cp\u003eDetection of MSAs included: anti-EJ, anti-HMGCR, anti-Jo-1, anti-MDA5, anti-Mi-2, anti-NXP2, anti-OJ, anti-PL-7, anti-PL-12, anti-SAE, anti-SRP, and anti-TIF1-γ. Detection of MAAs included: anti-Ku, anti-PM-Scl 75, anti-PM-Scl 100, and anti-Ro52. Analysis was detected by immunoblot (Euroline Myositis Profile 3 Immunoline-blot, Euroimmun, Germany) as previously reported [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eMuscle pathology\u003c/h2\u003e \u003cp\u003eMuscle biopsies were obtained from the quadricep of 15 patients from Nanfang Hospital. Serial 5-\u0026micro;m frozen sections were collected and stained with hematoxylin-eosin, NADH-tetrazolium reductase, modified Gomori\u0026rsquo;s trichrome, periodic acid-Schiff (PAS), oil red O (ORO), succinate dehydrogenase, and cytochrome C oxidase. Immunohistochemistry staining was performed for: dysferlin, dystrophin, α-sarcoglycans to δ-sarcoglycans, major histocompatibility complex class Ⅰ (MHC-Ⅰ), CD4, CD8, CD68, CD79, and the membrane attack complex (MAC).\u003c/p\u003e \u003cp\u003eMuscle biopsies were assessed for the following three aspects; myo-fiber type pathology, muscle tissue pathology, and inflammation. For myo-fiber pathology, the percentage of myo-fibers with atrophy, necrosis, regeneration, heterogeneity (defined as the totality of myo-fibers with atrophy, necrosis, and regeneration) and central nucleus were assessed, by manually counting the total number of myo-fibers. Muscular tissue pathology included the following aspects: perimysial atrophy, endomysial fibrosis, and vasculitis. The characteristics of inflammation were categorized into: 1) the distribution of inflammatory cell as endomysial and/or perimysial; 2) the distribution of MAC deposition as on sarcolemma and/or capillaries; 3) the distribution of MHC-Ⅰ as focal or diffuse.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and prognosis\u003c/h2\u003e \u003cp\u003eAll patients received treatment that included: mono therapy with glucocorticoids (GC), dual therapy with GC and immunosuppressives (IS), as well as triple therapy with GC, IS and intravenous immunoglobulin (IVIg). Response to treatment was recorded as improvement in manual muscle testing (MMT-8) and reduction in CK [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. Since there is no consensus definition of IIM remission, the patient\u0026rsquo;s condition was recorded as disease activity with remission based on changes in CK and MMT-8. Since there is no consensus standard for evaluation of a patient\u0026rsquo;s prognosis, we defined patients who had remission as (CK reduced to \u0026le;\u0026thinsp;500 IU/L and/or MMT-8 score improved\u0026thinsp;\u0026ge;\u0026thinsp;5) and no relapse as a good prognosis. Patients with disease activity or relapsed after short-time remission were defined as a poor prognosis. Duration of observation was limited to 9 months.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eGenetic testing\u003c/h2\u003e \u003cp\u003eSuspected LGMD patients from our hospital received whole exome sequence (WES) testing at Nanfang Hospital. Genomic DNA was extracted from patients\u0026rsquo; blood or muscle tissue.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eSPSS software (version 24.0; IBM Corp., Armonk, USA) was used for statistical analysis. Qualitative variables were expressed as percentage and absolute frequency, with quantitative variables reported as means\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation. Comparison of qualitative data was performed by Chi-squared test or Yate\u0026rsquo;s correction test or Fisher\u0026rsquo;s exact test. Comparison of quantitative data between two independent samples was performed by Mann-Whitney U test or Student\u0026rsquo;s t test (two-tailed). Analysis of multiple independent samples was performed by ANOVA or Kruskal-Wallis test. Furthermore, univariable Logistic Regression was used to identify prognosis predictors. Variables with \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.1 were included in the multivariable model. Multivariable Logistic Modeling was used to identify independent predictors of prognosis. Overall, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significantly different.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eClinical features of anti-HMGCR-positive IMNM patients\u003c/h2\u003e \u003cp\u003eWe identified 18 patients diagnosed with anti-HMGCR-positive IMNM. Clinical data are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical features and pathological manifestations of 18 patients with anti-HMGCR-positive IMNM\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eGender\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOnset age (y)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eDuration (m)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eStatins exposure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscular symptoms\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eExtra-muscular symptoms\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, myalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eRosuvastatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, myalgia, dysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eArthralgia, cardiac involvement, weight loss\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDyspnea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eILD, weight loss\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, myalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eRash\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e43\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, myalgia, dysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eArthralgia, rash, ILD, weight loss\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, dysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e45\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness, myalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eArthralgia, weight loss\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003econtinued\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMMT-8 score before/after therapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHighest CK(IU/L) before/after therapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAnti-HMGCR antibody titer\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eOther MSAs\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePrognosis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61/63\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11914/2856\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62/69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7202/1453\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e66/70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6865/2735\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3695/2534\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60/60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1164/195\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64/72\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4974/3113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71/76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9708/1594\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71/77\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3759/1105\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68/75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e589/199\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-NXP2, anti-Ku, anti-PM/Scl75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e65/73\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12555/1880\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-SRP, anti-SAE1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36/15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-Ro52, anti-PM/Scl75\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e75/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5215/620\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-SRP, anti-OJ, anti-Ro-52, ANA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e589/126\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-MDA5, anti-PL7, anti-Ro52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80/80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e862/519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-OJ, anti-Ku\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58/65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23462/3532\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-SRP, anti-Ro-52, ANA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69/74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16037/1320\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eanti-SRP\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eGood\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e49/49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2106/153\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e+++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS, IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54/61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21410/5253\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e++\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eGC, IS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003ePoor\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eANA\u003c/em\u003e anti-nuclear antibody, \u003cem\u003eCK\u003c/em\u003e creatine kinase, \u003cem\u003eGC\u003c/em\u003e glucocorticoid, \u003cem\u003eIS\u003c/em\u003e immunosuppressant, \u003cem\u003eIVIg\u003c/em\u003e intravenous immunoglobulin, \u003cem\u003eMMT-8\u003c/em\u003e manual muscle, \u003cem\u003eMSA\u003c/em\u003e myositis-specific antibodies\u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e continued\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"5\" nameend=\"c6\" namest=\"c2\"\u003e \u003cp\u003eMyofiber type pathology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eMyofiber type pathology\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c10\" namest=\"c8\"\u003e \u003cp\u003eMyofiber type pathology\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAtrophy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNecrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRegeneration\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eHeterogeneity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eCentral nucleus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eFeatures\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eInflammatory cell\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSarcolemma/\u003c/p\u003e \u003cp\u003eCapillary MAC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eMHC-Ⅰ\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e45%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eendomysial fibrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e43%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e27%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e14%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eperimysial atrophy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eperimysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/ +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eDiffuse\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/ +\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003evasculitis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eperimysium, endomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eperimysium, endomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e29%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eendomysial fibrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eperimysium, endomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient 18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eendomysial fibrosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eendomysium\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e+/-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eFocal\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eMAC\u003c/em\u003e membrane attack complex, \u003cem\u003eMHC-Ⅰ\u003c/em\u003e major histocompatibility complex Ⅰ, \u003cem\u003eNA\u003c/em\u003e not available.\u003c/p\u003e \u003cp\u003eThe age of onset for these patients ranged from 19 to 73 years of age (40.61\u0026thinsp;\u0026plusmn;\u0026thinsp;18.28 years). Eleven patients (11/18, 61.11%) were female and seven patients (7/18, 38.89%) were male. The median duration from symptom emergence to diagnosis for anti-HMGCR-positive IMNM was 9.50 months (1month-132 months).\u003c/p\u003e \u003cp\u003eSeventeen patients (17/18, 94.44%) complained of muscular symptoms, sixteen patients (16/18, 88.89%) had muscle weakness, five patients (5/18, 27.78%) had myalgia, and two patients (2/18, 11.1%) had dyspnea and two patients (2/18, 11.11%) had dysphagia. Seven patients (7/18, 38.9%) had extra-muscular symptoms. Among them, four patients (4/18, 22.22%) had arthralgia and four patients (4/18, 22.22%) had weight loss, three patients (3/18, 16.67%) had a rash, two patients (2/18, 11.11%) had interstitial lung disease (ILD), and one patient (1/18, 5.56%) had cardiac involvement. Nasopharyngeal carcinoma was found in one patient (1/18, 5.56%) during outpatient follow-up. One patient (1/18, 5.56%) had an exposure history to rosuvastatin.\u003c/p\u003e \u003cp\u003eAll patients were evaluated for muscle strength based on the MMT-8. The score for theMMT-8 ranged from 49 to 80 (65.94\u0026thinsp;\u0026plusmn;\u0026thinsp;8.17). CK levels were elevated in 17 patients (17/18, 94.44%), while one patient (1/18, 5.56%) remained normal. The serum CK level ranged from 36 to 23462 IU/L (7341.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7177.24 IU/L).\u003c/p\u003e \u003cp\u003eAnti-HMGCR was strongly positive (+++) for ten patients (10/18, 55.56%), moderately positive (++) for four patients (4/18, 22.22%) and weakly positive (+) for four patients (4/18, 22.22%). Anti-HMGCR antibody overlap with other antibodies was observed in eight patients (8/18, 44.44%). The coexistence of anti-HMGCR antibody with one or more MSA and/or MAA was detected in all eight of these patients (8/18, 44.44%), including anti-SAE1 antibody (1/8, 12.50%), anti-MDA5 antibody (1/8, 12.50%), anti-NXP2 antibody (1/8, 12.50%), anti-PL-7 antibody (1/8, 12.50%), anti-Ku antibody (2/8, 25.00%), anti-OJ antibody (2/8, 25.00%), anti-PM-Scl-75 antibody (2/8, 25.00%), anti-Ro-52antibody (4/8, 50.00%), and anti-SRP antibody (4/8, 50.00%). ANA were detected in two patients (2/8, 25.00%).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePathologic manifestations of anti-HMGCR-positive IMNM patients\u003c/h2\u003e \u003cp\u003eMuscle biopsy results for 15 patients are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. As for myo-fiber type pathology, the percentage of myo-fibers with atrophy, necrosis, regeneration, heterogeneity, and central nucleus was a range of 2%-34%, 0\u0026ndash;19%, 1%-15%, 9\u0026ndash;45%, and 1%-22%, respectively.\u003c/p\u003e \u003cp\u003eRegarding muscle tissue pathology, three patients (3/15, 20.00%) had endomysial fibrosis, three patients (3/15, 20.00%) had vasculitis, one patient (1/15, 6.67%) had perimysial atrophy.\u003c/p\u003e \u003cp\u003eWith respect to inflammation, eleven patients (11/15, 73.33%) had endomysial inflammatory cell infiltration, while four patients (4/15, 26.67%) had perimysial inflammatory cell infiltration. Fourteen patients (14/15, 93.33%) had focal distribution of MHC-Ⅰ, while one patient (1/15, 6.67%) had diffuse distribution of MHC-Ⅰ. Sarcolemma MAC deposition was observed in all muscle biopsies (15/15, 100.00%), while capillary MAC positivity was only observed in two patients (2/15, 13.33%). Immunohistochemistry showed that CD4\u003csup\u003e+\u003c/sup\u003e T cells, CD8\u003csup\u003e+\u003c/sup\u003e T cells, and CD68\u003csup\u003e+\u003c/sup\u003e macrophages were the most common inflammatory cells. No diagnostic mutations of known LGMD associated proteins were observed by immunostaining.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTreatment and response of anti-HMGCR-positive IMNM patients\u003c/h2\u003e \u003cp\u003eAll 18 patients received treatment (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Nine patients (9/18, 50.00%) were treated with dual-therapy of GC and IS. Seven patients (7/18, 38.89%) received triple-therapy of GC, IS, and IVIg. Two patients (2/18, 11.11%) received mono-therapy with GC. After treatment, myalgia and extra-muscular symptoms disappeared in all patients. All patients had a reduction in CK. Serum CK levels after treatment ranged from 15 to 5253 IU/L (1622.33\u0026thinsp;\u0026plusmn;\u0026thinsp;1462.54 IU/L), with a reduction range of 31.42%-92.74% (71.29%\u0026plusmn;18.86%). Except for two patients with normal muscle strength, 14 patients (14/18, 77.8%) had variable muscle strength development, while two patients (2/18, 11.11%) exhibited stabilization. MMT-8 scores after treatment varied from 49 to 80 (70.94\u0026thinsp;\u0026plusmn;\u0026thinsp;8.50), with an improvement variation of 0\u0026ndash;16 (5.00\u0026thinsp;\u0026plusmn;\u0026thinsp;3.99).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eComparison of non-overlap and overlap anti-HMGCR-positive IMNM patients\u003c/h2\u003e \u003cp\u003eWe collected clinical data for 50 patients diagnosed with anti-HMGCR-positive IMNM who had been reported in previous studies as well as 18 patients from our hospital.\u003c/p\u003e \u003cp\u003eSince the presence of anti-HMGCR antibody and other antibodies resulted in different clinical features, we separated patients into two subgroups: non-overlap anti-HMGCR-positive IMNM patients and overlap anti-HMGCR-positive IMNM patients.\u003c/p\u003e \u003cp\u003eThe comparison of clinical data for these two subgroups is presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compared to overlap anti-HMGCR-positive IMNM patients, earlier onset age (36.65\u0026thinsp;\u0026plusmn;\u0026thinsp;18.70 vs 46.14\u0026thinsp;\u0026plusmn;\u0026thinsp;17.48, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038) and longer disease duration (56.25\u0026thinsp;\u0026plusmn;\u0026thinsp;80.58 vs11.53\u0026thinsp;\u0026plusmn;\u0026thinsp;19.19, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) were found in non-overlap patients. Moreover, non-overlap anti-HMGCR patients had a higher frequency of muscle weakness (100.00% vs 75.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), but a lower prevalence of myalgia (17.50% vs 46.43%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.010) and dyspnea (0.00% vs 25.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001), with lower MMT-8 scores (63.44\u0026thinsp;\u0026plusmn;\u0026thinsp;7.21 vs 71.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.14, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.004) than overlap patients. With regard to extra-muscular symptoms, overlap anti-HMGCR-positive IMNM patients had a higher prevalence of extra-muscular symptoms (89.29% vs 17.50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), including ILD (28.57% vs 2.50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003), arthralgia (32.10% vs 0.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0001), weight (25.00% vs 2.50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.014), and skin involvement (53.57% vs 15.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) than non-overlap patients. Overlap anti-HMGCR-positive IMNM patients had a lower frequency of treatment with IVIg (9.50% vs 60.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001) than non-overlap patients. Correlations between overlap antibodies and muscular and extra-muscular symptoms in overlap anti-HMGCR-positive IMNM patients are shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. With regard to muscular symptoms, limb muscle weakness was predominantly presented in patients except for patients with anti-MDA5 antibody, all of which (5/5, 100.0%) complained of dyspnea, and patients with anti-PM-Scl-75 antibody presenting with dysphagia (2/3, 66.67%). Myalgia was shown in all patients with anti-Ku antibody (3/3, 100.00%) and anti-OJ antibody (2/2, 100.00%). As for extra-muscular symptoms, all patients with anti-MDA5 antibody (5/5, 100.00%) showed skin involvement and ILD. Most patients with anti-Jo-1 antibody (2/3, 66.67%) presented with ILD and arthralgia.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical features between non-overlap and overlap patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-overlap (n\u0026thinsp;=\u0026thinsp;40)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eOverlap (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23/36 (63.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16 (57.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.583\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset age (years old)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36.65\u0026thinsp;\u0026plusmn;\u0026thinsp;18.70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46.14\u0026thinsp;\u0026plusmn;\u0026thinsp;17.48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.038\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56.25\u0026thinsp;\u0026plusmn;\u0026thinsp;80.58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.53\u0026thinsp;\u0026plusmn;\u0026thinsp;19.19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMT-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e63.44\u0026thinsp;\u0026plusmn;\u0026thinsp;7.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.77\u0026thinsp;\u0026plusmn;\u0026thinsp;7.14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.004\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHighest CK (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7401.54\u0026thinsp;\u0026plusmn;\u0026thinsp;5616.61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8470.60\u0026thinsp;\u0026plusmn;\u0026thinsp;7289.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscular symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (75.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (17.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (46.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.097\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtra-muscular symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7 (17.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (89.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (32.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.014\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6 (15.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15 (53.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e \u003cp\u003eTreatment and outcomes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWith IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21/35 (60.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2/21 (9.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGood prognosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2/10 (20.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/8 (87.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eCK\u003c/em\u003e creatine kinase, \u003cem\u003eILD\u003c/em\u003e interstitial lung disease, \u003cem\u003eIVIg\u003c/em\u003e intravenous immunoglobulin, \u003cem\u003eMMT-8\u003c/em\u003e manual muscle testing. \u003csup\u003e*\u003c/sup\u003e \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe muscular and extra-muscular symptoms in all overlap anti-HMGCR-positive IMNM patients. The heatmap showed the percentage of muscular and extra-muscular symptoms in patients with different overlap antibodies. With regard to muscular symptoms, limb muscle weakness was predominantly presented in patients except for patients Anti-MDA5 antibody complaining of with dyspnea (5/5, 100.00%) and anti-PM-Scl-75 antibody of dysphagia (2/3, 66.67%). Myalgia was shown in all patients with anti-Ku antibody (3/3, 100.00%) and anti-OJ antibody (2/2, 100.00%). As for extra-muscular symptoms, all patients with anti-MDA5 antibody (5/5, 100.00%) showed skin involvement and ILD. Most patients with anti-Jo-1 antibody (2/3, 66.67%) presented with ILD and arthralgia.\u003c/p\u003e \u003cp\u003eComparison of the 15 biopsies from non-overlap and overlap anti-HMGCR-positive IMNM patients from our hospital is shown (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). As for myo-fiber type pathology, non-overlap anti-HMGCR-positive IMNM patients had a higher percentage of myo-fibers with atrophy (15.22%\u0026plusmn;7.79% vs 5.50%\u0026plusmn;3.02%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), central nucleus (9.22%\u0026plusmn;9.40% vs 1.33%\u0026plusmn;0.52%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) and heterogeneity (31.11%\u0026plusmn;10.69% vs 17.50%\u0026plusmn;6.95%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017) compared to overlap patients. No statistically significant difference was observed in myo-fibers with necrosis (8.33%\u0026plusmn;5.61% vs 4.83%\u0026plusmn;4.96%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.238) and regeneration (7.56%\u0026plusmn;3.47% vs 7.17%\u0026plusmn;5.67%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.871). For muscle tissue pathology, we found no significant difference in the prevalence of perimysial atrophy (0.00% vs 16.67%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.400), endomysial fibrosis (33.33% vs 0.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.229), or vasculitis (11.11% vs 16.67%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000) between overlap and non-overlap anti-HMGCR-positive IMNM patients. With regard to inflammatory pathology, there was no difference in endomysial inflammatory cell infiltration (88.89% vs 50.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.235), perimysial inflammatory cells infiltration (11.11% vs 50.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.235), the focal distribution of MHC-Ⅰ (100.00% vs 83.33%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.400), sarcolemma MAC deposit (100.00% vs 100.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.000), or capillary MAC deposit (0.00% vs 33.33%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.143) between non-overlap and overlap anti-HMGCR-positive IMNM patients.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eComparison of non-overlap and overlap anti-HMGCR-positive IMNM patient pathologic manifestations. For myo-fiber pathology, non-overlap anti-HMGCR-positive IMNM presented with a higher percentage of myo-fibers with atrophy (15.22%\u0026plusmn;7.79% vs 5.50%\u0026plusmn;3.02%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.013), central nucleus (9.22%\u0026plusmn;9.40% vs 1.33%\u0026plusmn;0.52%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028) and heterogeneity (31.11%\u0026plusmn;10.69% vs 17.50%\u0026plusmn;6.95%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017) compared to overlap patients. For muscle tissue pathology and inflammatory pathology, there were no significant differences.\u003c/p\u003e \u003cp\u003eDifferences in treatment between non-overlap and overlap anti-HMGCR-positive IMNM patients are shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Non-overlap anti-HMGCR-positive IMNM patients had a higher frequency of IVIg use than overlap patients (60.00% vs 9.50%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e \u003cp\u003eResponse to the treatment is presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eA, B. Compared with non-overlap anti-HMGCR-positive IMNM patients, overlap patients had greater improvement (8.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.10 vs 4.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047) in MMT-8 scores after treatment. However, there was no significant difference in the percentage of CK reduction (69.05%\u0026plusmn;20.22% vs 74.10%\u0026plusmn;17.94%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.588) between non-overlap and overlap anti-HMGCR-positive IMNM patients. Additionally, overlap anti-HMGCR-positive IMNM patients had a higher prevalence of a good prognosis than non-overlap patients (87.50% vs 20.00%, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.015) (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eA comparison of patients with a good and a poor prognosis was performed. Anti-HMGCR-positive IMNM patients who had a good prognosis had higher MMT-8 scores compared to patients who had a poor prognosis (69.67\u0026thinsp;\u0026plusmn;\u0026thinsp;6.98 vs 62.22\u0026thinsp;\u0026plusmn;\u0026thinsp;7.87, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.050) (\u003cb\u003eSuppl. Table\u0026nbsp;1\u003c/b\u003e). By univariable analysis, overlap antibody (B\u0026thinsp;=\u0026thinsp;28.0, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) was found to be a good prognostic predictor, while MMT-8 score was not (B\u0026thinsp;=\u0026thinsp;1.2, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.079). By multivariable analysis, overlap antibody (B\u0026thinsp;=\u0026thinsp;28.0, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012) was identified as an independent predictor of a good prognosis (\u003cb\u003eSuppl. Table\u0026nbsp;2\u003c/b\u003e). ROC analysis demonstrated a good performance for overlap antibody as a predictor of prognosis, with an AUC of 0.833 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017, 95%CI, 0.629-1.000) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003eC). A cut-off value (1.50) had a sensitivity of 77.8% and specificity of 88.9%.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTreatment response and prognosis for non-overlap and overlap anti-HMGCR-positive IMNM patients. (\u003cb\u003eA\u003c/b\u003e) Percentage of CK reduction: there was no significant difference between non-overlap and overlap patients. (\u003cb\u003eB\u003c/b\u003e) MMT-8 improvement: overlap patients had greater improvement in MMT-8 scores after treatment (8.00\u0026thinsp;\u0026plusmn;\u0026thinsp;4.10 vs 4.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.90, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047) than non-overlap patients. (\u003cb\u003eC\u003c/b\u003e) The area under curve (AUC) values indicate that overlap antibody can serve as a predictor of a good prognosis, with an AUC of 0.833 (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017, 95%CI, 0.629-1.000). A cut-off value (1.50) had a sensitivity of 77.8% and specificity of 88.9%. Error bar =\u0026thinsp;Standard deviation. \u003csup\u003e*\u003c/sup\u003e\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eComparison of non-LGMD-like and LGMD-like anti-HMGCR-positive IMNM patients\u003c/h2\u003e \u003cp\u003eAmong the patients diagnosed with non-overlap anti-HMGCR-positive IMNM, a special type of disease resembling LGMD has been identified that does not have an associated pathogenic gene. To demonstrate whether the LGMD-like anti-HMGCR-positive IMNM is a unique subtype of non-overlap anti-HMGCR-positive IMNM, we separated non-overlap anti-HMGCR-positive IMNM patients into two phenotypes: non-LGMD-like anti-HMNGCR-positive IMNM and LGMD-like anti-HMNGCR-positive IMNM. Comparisons were made of the clinical-pathologic characteristics of the two phenotypes (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eWith regard to clinical characteristics, LGMD-like anti-HMGCR-positive IMNM patients had an earlier age of onset (21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;14.13 vs 44.68\u0026thinsp;\u0026plusmn;\u0026thinsp;16.94, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), longer duration (128.75\u0026thinsp;\u0026plusmn;\u0026thinsp;97.92 vs 15.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.80, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), and lower MMT-8 scores (51.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54 vs 68.33\u0026thinsp;\u0026plusmn;\u0026thinsp;7.21 \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) than non-LGMD-like patients.\u003c/p\u003e \u003cp\u003eWith regard to myo-fiber type pathology, LGMD-like anti-HMGCR-positive patients exhibited profound myo-fibers with atrophy and predominant myo-fibers with the central nucleus, resembling muscular dystrophy more than the shared characteristics of severe myo-fiber necrosis and regeneration (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). There was no remarkable difference with regard to muscle tissue or inflammatory pathology. With regard to different types of CD staining for T lymphocytic cell, there were also no significant differences.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of clinical features between non-LGMD-like and LGMD-like patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNon-LGMD-like (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLGMD-like (n\u0026thinsp;=\u0026thinsp;12)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eClinical data\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (64.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4/8 (50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.683\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOnset age (years old)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.68\u0026thinsp;\u0026plusmn;\u0026thinsp;16.94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.33\u0026thinsp;\u0026plusmn;\u0026thinsp;14.13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration (months)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15.90\u0026thinsp;\u0026plusmn;\u0026thinsp;28.80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e128.75\u0026thinsp;\u0026plusmn;\u0026thinsp;97.92\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.0001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMMT-8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68.33\u0026thinsp;\u0026plusmn;\u0026thinsp;7.21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.50\u0026thinsp;\u0026plusmn;\u0026thinsp;3.54\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.003\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHighest CK (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7160.65\u0026thinsp;\u0026plusmn;\u0026thinsp;5629.42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10339.50\u0026thinsp;\u0026plusmn;\u0026thinsp;8150.56\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eClinical symptoms\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscular symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMuscle weakness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (100.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyalgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.081\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyspnea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysphagia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eExtra-muscular symptoms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (21.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.586\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthralgia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLoss of weight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSkin involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (17.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (8.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.772\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"4\" nameend=\"c4\" namest=\"c1\"\u003e \u003cp\u003eTreatment\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWith IVIg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11/23 (47.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7/8 (87.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.095\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cem\u003eCK\u003c/em\u003e creatine kinase, \u003cem\u003eILD\u003c/em\u003e interstitial lung disease, \u003cem\u003eIVIg\u003c/em\u003e intravenous immunoglobulin, \u003cem\u003eMMT-8\u003c/em\u003e manual muscle testing. \u003csup\u003e*\u003c/sup\u003e \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePathological manifestations of LGMD-like (\u003cb\u003eA\u003c/b\u003e-\u003cb\u003eC\u003c/b\u003e) and non-LGMD-like anti-HMGCR-positive IMNM patients (\u003cb\u003eD\u003c/b\u003e-\u003cb\u003eF\u003c/b\u003e). LGMD-like patient\u0026rsquo;s biopsy showed profound myo-fibers with atrophy (black arrowhead) and central nucleus (black arrow) (\u003cb\u003eA\u003c/b\u003e) and focal CD4 (black arrow) (\u003cb\u003eB\u003c/b\u003e) and CD68 lymphocytic infiltration (black arrow) (\u003cb\u003eC\u003c/b\u003e). Non-LGMD-like patient\u0026rsquo;s biopsy showed predominant myo-fibers with necrosis and regeneration (white arrow) (\u003cb\u003eD\u003c/b\u003e) and scattered CD4 lymphocytic infiltration (black arrow) (\u003cb\u003eE\u003c/b\u003e) and focal CD68 lymphocytic infiltration (black arrow) (\u003cb\u003eF\u003c/b\u003e). Scale bar =\u0026thinsp;100 \u0026micro;m.\u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, we collected clinical and pathologic data from anti-HMGCR-positive IMNM patients in our hospital and similar patient data from previous studies. In this manner we developed an essential and easily available clinical-pathological classification of anti-HMGCR-positive IMNM.\u003c/p\u003e \u003cp\u003eAnti-HMGCR antibody was previously considered distinguishable in that they are mutually exclusive in patients [\u003cspan additionalcitationids=\"CR27\" citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e], but a growing number of anti-HMGCR-IMNM patients with the coexistence of other MSAs has been reported, with unusual symptoms [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Likewise, nearly half anti-HMGCR-positive IMNM patients admitted to our hospital had antibodies other than anti-HMGCR antibody, exhibiting distinguishable symptoms. Therefore, we evaluated the coexistence of anti-HMGCR antibody and other antibodies appears to be associated with unique clinical and pathological features, suggesting the possibility of a universal phenomenon.\u003c/p\u003e \u003cp\u003eDifferent from the conventional symptoms of non-overlap anti-HMGCR-positive IMNM, in our study, the overlap anti-HMGCR-positive IMNM was found to more resemble dermatomyositis, presenting with muscle weakness and extra-muscular symptoms, while extra-muscular symptoms in overlap patients mostly corresponded to MSAs other than anti-HMGCR antibody. Similar to the previous studies, overlap anti-HMGCR-positive IMNM patients with anti-ARS antibodies generally showed anti-synthetase syndrome [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e], while patients with anti-MDA antibody commonly presented as skin involvement and ILD [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Despite the striking similarity to DM clinical symptoms, nearly all muscle biopsies of patients with overlap anti-HMGCR-positive IMNM conformed to the manifestation of IMNM [\u003cspan additionalcitationids=\"CR15\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. As a result, overlap anti-HMGCR-positive IMNM is probably a special sub-type of anti-HMGCR-positive IMNM, presenting with both dermatomyositis-like clinical features and pathological manifestations, indicating immune-mediated necrotizing myopathy. Consequently, we hypothesize that for overlap anti-HMGCR-positive IMNM patients, anti-HMGCR antibody plays a dominant role in muscle injury, while other antibodies associate with extra-muscular symptoms.\u003c/p\u003e \u003cp\u003eInterestingly, few overlap patients complained of dyspnea or dysphagia, without limb muscle weakness, especially in patients with anti-MDA5 patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Moreover, higher MMT-8 score or nearly normal muscle strength in overlap anti-HMGCR-positive IMNM patients can be explained by a lower percentage of myo-fibers with atrophy and heterogeneity, because of reduced muscle injury. The likely reason is that anti-HMGCR is not the important antibody when other MSAs are present.\u003c/p\u003e \u003cp\u003eTherapy and treatment responses were compared for overlap and non-overlap anti-HMGCR-positive IMNM patients. Nearly all patients with overlap anti-HMGCR IMNM received dual therapy with GC and IS, while half of non-overlap patients required triple therapy of GC, IS, and IVIg, which prevented worsening symptoms. Post-treatment MMT-8 score improvement was significantly higher in overlap anti-HMGCR IMNM patients, indicating that overlap patients may respond well to dual therapy, while non-overlap anti-HMGCR-positive IMNM patients may have a relatively limited response to such treatment. In terms of prognosis, overlap anti-HMGCR-positive IMNM patients tend to have a good prognosis compared to non-overlap patients. This may be explained by weakly or moderately positive anti-HMGCR antibody existing in most overlap patients. As such, differing clinical-pathological features suggest that the mechanism of pathogenesis of it is probably different, but such an assertion requires further investigation.\u003c/p\u003e \u003cp\u003eLGMD-like anti-HMGCR-positive IMNM patients (who always have only anti-HMGCR antibody) are typically children and teenagers with a chronic and progressive disease course [\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In addition to negative family history and negative genetic testing results, none of the patients diagnosed with LGMD-like anti-HMGCR-positive IMNM complained of myalgia, although a few patients exhibited extra-muscular symptoms. Consistent with the published literature, pathological manifestations of this subtype were distinguished by considerable atrophic myo-fibers and predominant myo-fibers with central nucleus [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. However, confirmation of these results requires assessment of more LGMD-like anti-HMGCR-positive IMNM patients. Myo-fiber heterogeneity, together with endomysial fibrosis found in the LGMD-like subtype, can likely be explained by the chronicity of the process. Considering the peculiar clinical and special pathological manifestations, we speculate a distinctive pathogenesis for LGMD-like anti-HMGCR-positive IMNM patients with the possibility of genetic factor involvement.\u003c/p\u003e \u003cp\u003eThere are limitations to this study. First, this study is retrospective for anti-HMGCR-positive IMNM patients, so information bias is inevitable. Second, a limited number of anti-HMGCR-positive IMNM patients, especially LGMD-like anti-HMGCR-positive IMNM patients were constraint for this study. Finally, proteomics, transcriptomics, and metabolomics analysis is essential for a more complete evaluation of the involved mechanisms of pathogenesis.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, we separated overlap anti-HMGCR-positive IMNM patients from non-overlap anti-HMGCR-positive IMNM patients based on the antibodies involved in extra-muscular symptoms and clinical and pathological characteristics. Differences among LGMD-like anti-HMGCR-positive IMNM patients indicated the probability that different subtypes exist within non-overlap anti-HMGCR-positive IMNM patients. However, classification confirmation of anti-HMGCR-positive IMNM patients requires further proteomics, transcriptomics and metabolomics analysis. Such analysis has the potential to provide individualized patient treatment.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003cstrong\u003eConflict of interest\u003c/strong\u003e \u003cp\u003eThe authors declare no conflict of interest.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eEthics approval\u003c/strong\u003e \u003cp\u003eThis study involves human participants and the study was approved by the Ethics Committee of Nanfang Hospital, Southern Medical University, Guangzhou 510515, China (No. NFEC-2023-130). The study followed the principles of the Declaration of Helsinki.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to participate\u003c/strong\u003e \u003cp\u003e As the data were anonymized and collected retrospectively, no informed consent from participants was required in accordance with the ethics committee.\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConsent to publish\u003c/strong\u003e \u003cp\u003eNot applicable.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eThe authors declare that no funds, grants, or other support were received during the preparation of this manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eStudy conception and design: HZ and QH. Acquisition of data: WL, YC and XH. Analysis and interpretation of data: WL, YC and XH. Writing of the manuscript: all authors. Critical revision of the manuscript for important intellectual content: all authors. All authors had access to the data, commented on the report drafts and approved the final submitted version.\u003c/p\u003e\u003ch2\u003eAcknowledgements\u003c/h2\u003e \u003cp\u003eWe would like to thank the patients, and study nurses who participated in this study\u003c/p\u003e\u003ch2\u003eData availability\u003c/h2\u003e \u003cp\u003eThe datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eTanboon J, Nishino I. Classification of idiopathic inflammatory myopathies: pathology perspectives. Curr Opin Neurol. 2019;32(5):704\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/WCO.0000000000000740\u003c/span\u003e\u003cspan address=\"10.1097/WCO.0000000000000740\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLuo YB, Mastaglia FL. Dermatomyositis, polymyositis and immune-mediated necrotising myopathies. Biochim Biophys Acta. 2015;1852(4):622\u0026ndash;32. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.bbadis.2014.05.034\u003c/span\u003e\u003cspan address=\"10.1016/j.bbadis.2014.05.034\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSasaki H, Kohsaka H. Current diagnosis and treatment of polymyositis and dermatomyositis. Mod Rheumatol. 2018;28(6):913\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1080/14397595.2018.1467257\u003c/span\u003e\u003cspan address=\"10.1080/14397595.2018.1467257\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHoogendijk JE, Amato AA, Lecky BR et al. 119th ENMC international workshop: trial design in adult idiopathic inflammatory myopathies, with the exception of inclusion body myositis, 10\u0026ndash;12 October 2003, Naarden, The Netherlands. Neuromuscul Disord. 2004;14(5):337\u0026ndash;345. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nmd.2004.02.006\u003c/span\u003e\u003cspan address=\"10.1016/j.nmd.2004.02.006\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChristopher-Stine L, Casciola-Rosen LA, Hong G, Chung T, Corse AM, Mammen AL. A novel autoantibody recognizing 200-kd and 100-kd proteins is associated with an immune-mediated necrotizing myopathy. Arthritis Rheum. 2010;62(9):2757\u0026ndash;66. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/art.27572\u003c/span\u003e\u003cspan address=\"10.1002/art.27572\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMammen AL, Chung T, Christopher-Stine L, et al. Autoantibodies against 3-hydroxy-3-methylglutaryl-coenzyme A reductase in patients with statin-associated autoimmune myopathy. Arthritis Rheum. 2011;63(3):713\u0026ndash;21. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/art.30156\u003c/span\u003e\u003cspan address=\"10.1002/art.30156\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllenbach Y, Mammen AL, Benveniste O, Stenzel W, Immune-Mediated Necrotizing Myopathies Working Group. 224th ENMC International Workshop:: Clinico-sero-pathological classification of immune-mediated necrotizing myopathies Zandvoort, The Netherlands, 14\u0026ndash;16 October 2016. Neuromuscul Disord. 2018;28(1):87\u0026ndash;99. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.nmd.2017.09.016\u003c/span\u003e\u003cspan address=\"10.1016/j.nmd.2017.09.016\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBarrons R. Statin-Associated Autoimmune Myopathy: Review of the Literature. J Pharm Pract. 2023;36(2):383\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1177/08971900211040291\u003c/span\u003e\u003cspan address=\"10.1177/08971900211040291\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePrieto-Pe\u0026ntilde;a D, Ocejo-Vinyals JG, Mazariegos-Cano J, et al. Epidemiological and genetic features of anti-3\u0026ndash;hydroxy-3-methylglutaryl-CoA reductase necrotizing myopathy: Single-center experience and literature review. Eur J Intern Med. 2022;101:86\u0026ndash;92. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.ejim.2022.04.017\u003c/span\u003e\u003cspan address=\"10.1016/j.ejim.2022.04.017\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGe Y, Lu X, Peng Q, Shu X, Wang G. Clinical Characteristics of Anti-3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Antibodies in Chinese Patients with Idiopathic Inflammatory Myopathies. PLoS ONE. 2015;10(10):e0141616. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0141616\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0141616\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Published 2015 Oct 28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWatanabe Y, Suzuki S, Nishimura H, et al. Statins and myotoxic effects associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase autoantibodies: an observational study in Japan. Med (Baltim). 2015;94(4):e416. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000000416\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000000416\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLimaye V, Bundell C, Hollingsworth P, et al. Clinical and genetic associations of autoantibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme a reductase in patients with immune-mediated myositis and necrotizing myopathy. Muscle Nerve. 2015;52(2):196\u0026ndash;203. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/mus.24541\u003c/span\u003e\u003cspan address=\"10.1002/mus.24541\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTiniakou E, Pinal-Fernandez I, Lloyd TE, et al. More severe disease and slower recovery in younger patients with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase-associated autoimmune myopathy. Rheumatology (Oxford). 2017;56(5):787\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rheumatology/kew470\u003c/span\u003e\u003cspan address=\"10.1093/rheumatology/kew470\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang L, Wang L, Yang Y, et al. Coexistence of anti-HMGCR and anti-MDA5 identified by an unlabeled immunoprecipitation assay in a chinese patient cohort with myositis. Med (Baltim). 2018;97(47):e13236. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000013236\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000013236\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJiao Y, Cai S, Lin J, et al. Statin-na\u0026iuml;ve anti-HMGCR antibody-mediated necrotizing myopathy in China. J Clin Neurosci. 2018;57:13\u0026ndash;9. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1016/j.jocn.2018.08.010\u003c/span\u003e\u003cspan address=\"10.1016/j.jocn.2018.08.010\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzczesny P, Barsotti S, Nennesmo I, Danielsson O, Dastmalchi M. Screening for Anti-HMGCR Antibodies in a Large Single Myositis Center Reveals Infrequent Exposure to Statins and Diversiform Presentation of the Disease. Front Immunol. 2022;13:866701. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3389/fimmu.2022.866701\u003c/span\u003e\u003cspan address=\"10.3389/fimmu.2022.866701\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Published 2022 May 4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiang WC, Uruha A, Suzuki S, et al. Pediatric necrotizing myopathy associated with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibodies. Rheumatology (Oxford). 2017;56(2):287\u0026ndash;93. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1093/rheumatology/kew386\u003c/span\u003e\u003cspan address=\"10.1093/rheumatology/kew386\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMohassel P, Landon-Cardinal O, Foley AR, et al. Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. Neurol Neuroimmunol Neuroinflamm. 2018;6(1):e523. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1212/NXI.0000000000000523\u003c/span\u003e\u003cspan address=\"10.1212/NXI.0000000000000523\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Published 2018 Dec 12.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAllenbach Y, Drouot L, Rigolet A, et al. Anti-HMGCR autoantibodies in European patients with autoimmune necrotizing myopathies: inconstant exposure to statin. Med (Baltim). 2014;93(3):150\u0026ndash;7. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1097/MD.0000000000000028\u003c/span\u003e\u003cspan address=\"10.1097/MD.0000000000000028\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKishi T, Rider LG, Pak K, et al. Association of Anti-3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase Autoantibodies With DRB1*07:01 and Severe Myositis in Juvenile Myositis Patients. Arthritis Care Res (Hoboken). 2017;69(7):1088\u0026ndash;94. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/acr.23113\u003c/span\u003e\u003cspan address=\"10.1002/acr.23113\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVelardo D, Faravelli I, Cinnante C, Moggio M, Comi GP. Pediatric anti-HMGCR necrotizing myopathy: diagnostic challenges and literature review. Neurol Sci. 2020;41(10):3009\u0026ndash;13. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s10072-020-04491-6\u003c/span\u003e\u003cspan address=\"10.1007/s10072-020-04491-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTansley SL, Betteridge ZE, Simou S et al. Anti-HMGCR Autoantibodies in Juvenile Idiopathic Inflammatory Myopathies Identify a Rare but Clinically Important Subset of Patients [published correction appears in J Rheumatol. 2017;44(9):1417]. J Rheumatol. 2017;44(4):488\u0026ndash;492. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3899/jrheum.160871\u003c/span\u003e\u003cspan address=\"10.3899/jrheum.160871\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLundberg IE, Tj\u0026auml;rnlund A, Bottai M et al. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups [published correction appears in Ann Rheum Dis. 2018;77(9):e64]. Ann Rheum Dis. 2017;76(12):1955\u0026ndash;1964. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1136/annrheumdis-2017-211468\u003c/span\u003e\u003cspan address=\"10.1136/annrheumdis-2017-211468\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang H, Tian X, Zhang L, et al. Clinical and pathological features of immune-mediated necrotising myopathies in a single-centre muscle biopsy cohort. BMC Musculoskelet Disord. 2022;23(1):425. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1186/s12891-022-05372-z\u003c/span\u003e\u003cspan address=\"10.1186/s12891-022-05372-z\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Published 2022 May 6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRider LG, Koziol D, Giannini EH, et al. Validation of manual muscle testing and a subset of eight muscles for adult and juvenile idiopathic inflammatory myopathies. Arthritis Care Res (Hoboken). 2010;62(4):465\u0026ndash;72. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1002/acr.20035\u003c/span\u003e\u003cspan address=\"10.1002/acr.20035\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhirardello A, Gatto M, Franco C, et al. Detection of Myositis Autoantibodies by Multi-Analytic Immunoassays in a Large Multicenter Cohort of Patients with Definite Idiopathic Inflammatory Myopathies. Diagnostics (Basel). 2023;13(19):3080. Published 2023 Sep 28.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlenzi FM. Myositis Specific Autoantibodies: A Clinical Perspective. Open Access Rheumatol. 2020;12:9\u0026ndash;14. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.2147/OARRR.S231195\u003c/span\u003e\u003cspan address=\"10.2147/OARRR.S231195\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Published 2020 Jan 14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSatoh M, Tanaka S, Ceribelli A, Calise SJ, Chan EK. A Comprehensive Overview on Myositis-Specific Antibodies: New and Old Biomarkers in Idiopathic Inflammatory Myopathy. Clin Rev Allergy Immunol. 2017;52(1):1\u0026ndash;19. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1007/s12016-015-8510-y\u003c/span\u003e\u003cspan address=\"10.1007/s12016-015-8510-y\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHamaguchi Y, Fujimoto M, Matsushita T, et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS ONE. 2013;8(4):e60442. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.1371/journal.pone.0060442\u003c/span\u003e\u003cspan address=\"10.1371/journal.pone.0060442\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"idiopathic inflammatory myopathy, immune-mediated necrotizing myopathy, anti-HMGCR myopathy, anti-3-hydroxy-3-methylglutaryl coenzyme A reductase autoantibodies","lastPublishedDoi":"10.21203/rs.3.rs-4792955/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4792955/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAnti-HMGCR-positive immune-mediated necrotizing myopathy (IMNM) was initially considered as an exclusively skeletal muscular disease characterized by predominant proximal muscle weakness, observed in elderly patients with an acute duration. However, an increasing number of patients presented extra-muscular involvements coinciding with other autoimmune antibodies. Moreover, some juvenile patients showed chronic weakness of shoulder and hip girdle musculature, resembling limb-girdle muscular dystrophy (LGMD). The present study aims to develop the essential and easily available clinical-pathological classification for anti-HMGCR-positive IMNM patients. Eighteen anti-HMGCR-positive IMNM patients were from Nanfang Hospital and fifty were from published studies. We separated patients into two subgroups, including the overlap (with coexistence of other antibodies) and non-overlap groups (with only anti-HMGCR-positive patients). Medical information, including the clinical and pathological features, together with their treatments and prognosis were compared. We found that compared to the non-overlap anti-HMGCR-positive IMNM group, overlap patients had more extra-muscular symptoms, corresponding to the coexistence of other myositis-specific antibodies (MSAs) and resulting different treatments and prognoses. The early onset age and chronic process, together with the special pathology of resembling LGMD indicated that this is likely a different subtype in non-overlap anti-HMGCR-positive IMNM patients. The results revealed that the anti-HMGCR-positive IMNM patients can be separated into overlap and non-overlap anti-HMGCR-positive IMNM patients. The non-overlap group can be further divided into LGMD-like and non-LGMD-like anti-HMGCR-positive IMNM. However, the confirmed classification of anti-HMGCR-positive IMNM patients requires further proteomics and transcriptomics studies and could potentially be useful for individualized treatment decision making.\u003c/p\u003e","manuscriptTitle":"Clinical-pathologic classification of anti-HMGCR-positive immune-mediated necrotizing myopathy","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-28 02:35:48","doi":"10.21203/rs.3.rs-4792955/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"926c0a9c-ca40-4f77-8337-bcf070f91074","owner":[],"postedDate":"August 28th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-11T05:53:39+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-28 02:35:48","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4792955","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4792955","identity":"rs-4792955","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}