Features of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus

Features of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus | 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 Features of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus Qian Guo, Yang He, Xia Liu, Xu guang Gao, Jing Xu, Xue Li, Yue Sun, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-685756/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 We aimed to explore the clinical features and cerebral magnetic resonance imaging (MRI) changes of central nervous system demyelination in systemic lupus erythematosus (SLE) patients. Based on a consecutive cohort of 1191 SLE patients, 273 patients with cerebral MRI were enrolled to assess cerebral demyelination. Patients were divided into two groups, ie. complicated with or without demyelination. The MRI findings of the cerebral demyelination were divided into three categories: type A, periventricular white matter (WM) lesions; type B, subcortical WM lesions; type C, multiple discrete WM lesions. Among the 273 SLE patients with cerebral MRI, 35.9% (98/273) had demyelinating changes. The incidences of type A, B and C were 54.1% (53/98), 11.2% (11/98) and 92.9% (91/98), respectively. Fifty-one percent of the patients were with overlap of 2 or 3 types. Type C was the most common subgroup combined with other types. Compared with those without demyelination, the patients with demyelination were more likely to develop neuropsychiatric systemic lupus erythematosus (NPSLE), lupus nephritis (LN), hypertension and hyperuricemia ( p < 0.05). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with demyelination ( p < 0.05). In addition, the patients with demyelination had higher frequency of proteinuria and higher levels of CD8 + T cells ( p < 0.05). In multivariate logistic analysis, hyperuricemia and higher CD8 + T cells were significantly correlated with demyelination in SLE patients ( p < 0.05). The data suggest that demyelination is a common complication in SLE patients and strongly associated with systemic involvements, including NPSLE, LN, polyserous effusions and cardiac involvement. Hyperuricemia and higher CD8 + T cells were independent risk factors for demyelination in SLE. Health Economics & Outcomes Research Rheumatology Health Policy white matter (WM) systemic lupus erythematosus (SLE) magnetic resonance imaging (MRI) Introduction Systemic lupus erythematosus (SLE) is an autoimmune multi-system disease characterized by complex and varied clinical manifestations 1-4 . Neuropsychiatric manifestations appeared in about 37-90% of patients, including central, peripheral, autonomous nervous system and psychiatric involvement 5-7 , potentially with worse prognosis and mortality 8 . Demyelination is a term to describe a loss of the lipid-rich myelin sheaths with axons preserved relatively. It can not only invade the nervous system as primary demyelinating disorders, but also can be presented as a clinical manifestation of the autoimmune rheumatic disease. In SLE the demyelination of central nervous system (CNS) has been reported in about 0.3–2.7% 9-11 . Antinuclear antibodies (ANA) can be found in some primary demyelinating diseases, and anti-neuronal antibodies can also be found in SLE patients. The two can be independent of each other or overlap 12,13 . Demyelinating syndrome is one of the 19 defined syndromes in neuropsychiatric systemic lupus erythematosus (NPSLE) 14 with a prevalence of 1% and has been defined according to the presence of two or more manifestations of demyelinating disease 15 . However, demyelination in SLE patients is atypical and most of them are insufficient for the diagnosis of demyelinating syndrome. Since demyelinating lesions in SLE can be clinically silent and are not pathognomonic, it is not easy to detect the demyelination in the early stage. Meanwhile, treatment for demyelinating disease is also a clinical dilemma. There are few reports to analyze characteristics of demyelinating lesions of CNS in SLE patients. The aim of this study was to explore the clinical features and cerebral magnetic resonance imaging (MRI) changes of patients with SLE complicated with demyelination of CNS. Methods Study population. This retrospective monocentric study collected data from a consecutive cohort of 1191 patients with SLE who were hospitalized in the Department of Rheumatology and Immunology, Peking University People’s Hospital from July 2016 to January 2020. The diagnosis of SLE was based on 1997 revised American College of Rheumatology (ACR) classification criteria 16 . Of these patients, 273 underwent cerebral MRI owing to various reasons. Patients were divided into two groups: patients with and without demyelination which was determined by rheumatologist, neurologist and radiologist. All participants provided written informed consent (informed consent for participants < 18 years of age was obtained from a parent and/or legal guardian), in accordance with the Declaration of Helsinki. The research protocol was approved by the Institutional Research Ethics Committee of the Peking University People's Hospital (2019PHB007-01). Cerebral MRI scans. Cerebral MRI scans were performed on GE Signa HDxt 3.0 Tesla MRI scanner equipped with an 8-channel receive head coil and gradient coil field strength of 40mT/m. After three-plane positioning, sagittal T1-weighted images (WI) scan was performed, the front and back connections were used as the scan baseline, axial scan consisted of T1WI (TR/TE = 2390/10.688ms, FOV = 24cm, matrix 384×286), T2WI (TR/TE = 5200/107.408ms, matrix 320×320), T2WI-FLAIR (TR/TE = 7902/140.452ms, matrix 288×224). The scanning range was from the top of the skull to the foramen magnum, with a thickness of 5 mm and an interval of 1.5 mm. Diffusion-weighted imaging (DWI) used single-shot spin echo- planar imaging (TR/ TE = 5400/90.3ms, FOV = 24cm, matrix 128×128, NEX = 1), with copying the scan plane of axis sequence. Definition of cerebral MRI demyelinating lesions was: patchy or elongated T1-WI hypointense and T2-WI hyperintense lesions in periventricular white matter (WM), focal and patchy subcortical T1-WI hypointense and T2-WI hyperintense WM lesions, and/or multiple discrete, focal, small patchy or dotted cerebral T1-WI hypointense and T2-WI hyperintense WM lesions in brain, with no peripheral edema and space-occupying effect, except age, endocrine, nutritional and metabolic, hereditary or other interpretable diseases caused by small vessel disease. The MRI findings of the demyelination in SLE were divided into three categories: type A. patchy or elongated periventricular white matter (WM) lesions; type B. focal and patchy subcortical WM lesions; type C. multiple discrete, focal, small patchy or dotted WM lesions in brain. Clinical and laboratory assessment. General characteristics of patients were collected, including demographic data, disease duration, age at onset of symptoms, coexistence of other immune diseases, family history of immune disease, smoking history and drinking history. Complications included hypertension, diabetes, coronary heart disease, hyperlipidemia, hyperuricemia or cerebrovascular disease. NPSLE diagnosis was made according to the 1999 ACR case definitions for NPSLE syndromes (including central nervous involvement and peripheral neuropathy) 14 . Lupus nephritis (LN) was defined by the following criteria: a) persistent proteinuria greater than 0.5g per day, or b) the presence of granular, red cell, hemoglobin, tubular, or mixed casts. Hematological involvement was defined as white blood cell or platelet lower than normal value and autoimmune hemolytic anemia. Lung involvement contained interstitial lung disease, alveolar hemorrhage, pulmonary hypertension and others related with SLE. Digestive system involvement including intestinal pseudo-obstruction, protein-losing enteropathy, gastrointestinal bleeding, liver injury, pancreatitis and others due to SLE. Cardiac involvement was defined as cardiac manifestations related with SLE, including cardiomyopathy, heart valvular disease and others. Other clinical manifestations including fever (noninfectious fever), weight loss (weight loss༞5% within 1 month), arthritis, rash, photosensitivity, alopecia, aphthous ulcer, Raynaud phenomenon, myositis, pleuritis, pericarditis, polyserous effusions and retinopathy were recorded. Laboratory data included complete blood cell count, ANA, anti-double stranded DNA (ds-DNA) antibodies, anti-Sm antibodies, anti-SSA antibodies, anti-SSB antibodies, anti-RNP antibodies, anti-membrane DNA (mDNA) antibodies, anti-ribosomal Po (Rib-Po) antibodies, anti-nucleosome antibodies (ANUA), anti-β2 glicoprotein-I (β2-GPI) antibodies, anti-cardiolipin (aCL) antibodies, lupus anticoagulant (LA), Coomb’s test, rheumatoid factor (RF), proteinuria and levels of albuminuria, creatinine, erythrocyte sedimentation rate (ESR), IgG, IgA, IgM, complement 3 (C3), complement 4 (C4), total T cells percent, CD4 + T cells percent, CD8 + T cell percent and CD4 + T cells/CD8 + T cells. Statistical analysis. The Statistical Package for Social Sciences version23.0 (SPSS, Chicago, IL, USA) was performed to analyze the data. Continuous variables were presented as mean and standard deviation (SD) or median and interquartile range (IQR). Category data were presented as percentages. Differences between groups of continuous variables are analyzed by independent student’s t-test or non-parametric Wilcoxon Test. For categorical variables, Chi-squared test or non-parametric Fisher’s exact test were used to compare frequencies in different groups. Association between different clinical/laboratory variables and demyelination was studied using univariate and multivariate logistic regression models, the association measurement was shown as odds ratios (ORs) calculation, with its 95% confidence intervals (CI 95%). p value < 0.05 was regarded as statistically significant. Results Patients demographic characteristics. Of these 273 patients who underwent cerebral MRI, 91.2% were women, with a mean age of 38.7 ± 15.8 years and a median disease course of 5.0 (1.0, 13.0) years. The median age at onset of symptoms was 27 (21, 39) years. MRI findings of the demyelination in SLE. Among the 273 SLE patients with MRI, 98 had demyelinating changes, with 5 of them eligible for demyelinating syndrome (DS). Other patients have SLE-related demyelinating changes, but not DS. Of all the patients with demyelination, the incidences of type A, B and C were 54.1% (53/98), 11.2% (11/98) and 92.9% (91/98), respectively. Fifty-one percent of the patients were with overlap of 2 or 3 types and type C was the most common subgroup combined with other types. (Table 1 ). Type C and type A + C account for the majority of patients. Compared with those who performed as type C alone, patients with type A + C were tend to develop hypertension and peripheral neuropathy ( p < 0.05, respectively), and had longer disease duration and older age at onset of symptoms ( p < 0.05, respectively). Table 1 MRI findings of the demyelination in SLE. Type SLE with demyelination (n = 98) n % A 6 6.1 B 1 1.0 C 41 41.8 A + B 0 0 A + C 40 40.8 B + C 3 3.1 A + B + C 7 7.1 Clinical characteristics of SLE patients with demyelination. The clinical characteristics of patients with SLE were showed in Table 2 . Compared with those without demyelination, the patients with demyelination were more likely to develop NPSLE (including peripheral neuropathy and central nervous involvement) and LN ( p < 0.05, respectively). The types of NPSLE prone to occur in patients with demyelination included cerebrovascular disease, demyelinating syndrome, seizure disorders, cognitive dysfunction, autonomic disorder and polyneuropathy. Hypertension and hyperuricemia were the common complications ( p < 0.05). Patients with demyelination tend to have polyserous effusions and cardiac involvement ( p < 0.05). Table 2 Clinical characteristics of patients with SLE in different groups. NPSLE: systemic lupus erythematosus; LN: lupus nephritis. SLE with demyelination (n = 98) SLE without demyelination (n = 175) p -value General characteristics Female, n (%) 90 (91.8) 159 (90.9) 0.784 Age, median (IQR), years 41.0 (29.0,51.0) 27.5 (22.0,52.0) 0.088 Disease duration, median (IQR), years 6.0 (2.0,14.0) 4.0 (0.7,10.0) 0.207 Age at onset of symptoms, median (IQR), years 29.0 (23.0,40.0) 23.9 (19.0,39.0) 0.142 Coexistence of other immune diseases, n (%) 32 (32.7) 46 (26.3) 0.264 Family history of immune disease, n (%) 8 (8.2) 19 (10.9) 0.474 Smoking history, n (%) 5 (5.1) 14 (8.0) 0.367 Drinking history, n (%) 3 (3.1) 4 (2.3) 0.704 Complications Hypertension, n (%) 34 (34.7) 41 (23.4) 0.045 Diabetes, n (%) 6 (6.1) 14 (8.0) 0.568 Coronary heart disease, n (%) 1 (1.0) 9 (5.1) 0.101 Hyperlipidemia, n (%) 34 (34.7) 46 (26.3) 0.143 Hyperuricemia, n (%) 26 (26.5) 28 (16) 0.036 Cerebrovascular disease, n (%) 10 (10.2) 11 (6.3) 0.244 Clinical manifestations NPSLE, n (%) 58 (59.2) 70 (40) 0.002 Peripheral neuropathy, n (%) 22 (22.4) 13 (7.4) 0.001 Central nervous involvement, n (%) 53 (54.1) 64 (36.6) 0.005 LN, n (%) 52(53.1) 67 (38.3) 0.018 Lung involvement, n (%) 23 (23.5) 37 (21.1) 0.656 Cardiac involvement, n (%) 6 (6.1) 2 (1.1) 0.027 Digestive system involvement, n (%) 10 (10.2) 17 (9.7) 0.897 Hematological involvement, n (%) 85 (86.7) 137 (78.3) 0.086 Fever, n (%) 57 (58.2) 108 (61.7) 0.565 Weight loss, n (%) 19 (19.4) 39 (22.3) 0.574 Arthritis, n (%) 42 (42.9) 102 (58.3) 0.014 Rash, n (%) 55 (56.1) 114 (65.1) 0.141 Photosensitivity, n (%) 29 (29.6) 51 (29.1) 0.938 Alopecia, n (%) 48 (49) 90 (51.4) 0.698 Aphthous ulcer, n (%) 24 (24.5) 45 (25.7) 0.823 Raynaud phenomenon, n (%) 23 (23.5) 45 (25.7) 0.681 Myositis, n (%) 2 (2.0) 7 (4.0) 0.497 Pleuritis, n (%) 3 (3.1) 5 (2.9) 1.000 Pericarditis, n (%) 0 (0) 2 (1.1) 0.538 Polyserous effusions, n (%) 23 (23.5) 23 (13.1) 0.029 Retinopathy, n (%) 7 (7.1) 9 (5.1) 0.500 Comparison of laboratory findings of SLE patients with demyelination. In laboratory analysis, the patients with demyelination had higher frequency of proteinuria ( p < 0.05). In addition, higher levels of CD8 + T cells were found in patients with demyelination ( p < 0.05). There were less autoantibodies to ds-DNA, Sm and Rib-Po in the demyelination group, while was not significant statistically (Table 3 ). Table 3 Laboratory findings of patients with SLE in different groups. ANA: antinuclear antibodies; Anti-dsDNA: anti-double stranded DNA antibodies; Anti-Sm: anti-Sm antibodies; Anti-SSA: anti-SSA antibodies; Anti-SSB: anti-SSB antibodies; Anti-RNP: anti-RNP antibodies; Anti-mDNA: anti-membrane DNA antibodies; Rib-Po: anti-ribosomal Po antibodies; ANUA: anti-nucleosome antibodies; β2-GPI: anti-β2 glicoprotein-I antibodies; aCL: anti-cardiolipin antibodies; LA: lupus anticoagulant; RF: rheumatoid factor; ESR: erythrocyte sedimentation rate; C3: complement 3; C4: complement 4. SLE with demyelination (n = 98) SLE without demyelination (n = 175) p -value ANA, n (%) 91 (92.9) 170 (97.1) 0.125 Anti-dsDNA, n (%) 54 (55.1) 105 (60.0) 0.431 Anti-Sm, n (%) 14 (14.3) 40 (22.9) 0.088 Anti-SSA, n (%) 56 (57.1) 100 (57.1) 1.000 Anti-SSB, n (%) 15 (15.3) 19 (10.9) 0.286 Anti-RNP, n (%) 36 (36.7) 75 (42.9) 0.323 Anti-mDNA, n (%) 5 (5.1) 11 (6.3) 0.690 Rib-Po, n (%) 12 (12.2) 37 (21.1) 0.066 ANUA, n (%) 48 (49.0) 85 (48.6) 0.948 β2-GPI, n (%) 22 (22.4) 31 (17.7) 0.343 aCL, n (%) 27 (27.6) 38 (21.7) 0.277 LA, n (%) 29 (29.6) 37 (21.1) 0.118 Coomb’s test, n (%) 59 (60.2) 95 (54.3) 0.344 RF, n (%) 25 (25.5) 41 (23.4) 0.700 Proteinuria, n (%) 53 (54.1) 66 (37.7) 0.009 Albuminuria, median (IQR), g/day 0.360 (0.130,1.320) 0.185 (0.080,0.778) 0.005 Creatinine, median (IQR),µmol/L 58 (49.0,84.0) 54 (46.5,65.3) 0.208 ESR, median (IQR), mm/h 27.0 (11.0,63.0) 28 (11.0,53.0) 0.091 IgG, mean ± SD, g/L 15.952 ± 9.830 15.873 ± 7.085 0.944 IgA, mean ± SD, g/L 2.757 ± 2.897 2.609 ± 1.273 0.636 IgM, median (IQR), g/L 0.838 (0.42,1.47) 1.030 (0.677,1.485) 0.111 C3, median (IQR), g/L 0.625 (0.372,0.706) 0.504 (0.346,0.726) 0.851 C4, median (IQR), g/L 0.126 (0.074,0.156) 0.107 (0.568,0.146) 0.691 Total T cells, mean ± SD, % 72.72 ± 14.46 70.43 ± 14.50 0.345 CD4 + T cells, mean ± SD, % 30.00 ± 9.83 33.01 ± 11.34 0.100 CD8 + Tcells, mean ± SD, % 40.69 ± 13.60 34.97 ± 11.10 0.005 CD4 + T cells /CD8 + T cells, median (IQR) 0.67 (0.51,0.99) 0.94 (0.68,1,28) 0.005 Comparison of NPSLE patients with and without demyelination. In further analysis of the patients with NPSLE, those with demyelination were more likely to complicated with hypertension and hyperuricemia, and tend to have polyserous effusions, cardiac involvement, peripheral neuropathy, proteinuria and higher CD8 + T cells ( p < 0.05) (Table 4 ). Table 4 Comparison of NPSLE patients with and without demyelination. LN: lupus nephritis. SLE with demyelination (n = 58) SLE without demyelination (n = 70) p -value LN, n (%) 34 (58.6) 29 (41.4) 0.053 Hypertension, n (%) 22 (37.9) 12 (17.1) 0.008 Hyperuricemia, n (%) 16 (27.6) 8 (11.4) 0.020 Hyperlipidemia, n (%) 15 (25.9) 22 (31.4) 0.489 Weight loss, n (%) 10 (17.2) 23 (32.9) 0.044 Arthritis, n (%) 22 (37.9) 46 (65.7) 0.002 Rash, n (%) 30 (51.7) 53 (75.7) 0.005 Polyserous effusions, n (%) 16 (27.6) 8 (11.4) 0.020 Cardiac involvement, n (%) 4 (6.9) 0 (0) 0.040 Peripheral neuropathy, n (%) 21 (36.2) 13 (18.6) 0.025 Proteinuria, n (%) 38 (65.5) 25 (35.7) 0.001 CD8 + T cells, mean ± SD, % 43.619 ± 13.071 34.105 ± 10.825 0.001 Risk factors for demyelination in SLE patients. Univariate analysis suggested that SLE patients who had NPSLE, LN, hypertension, hyperuricemia, polyserous effusions, cardiac involvement, proteinuria and higher levels of CD8 + T cells were more likely to progress demyelination in brains ( p < 0.05). To further investigate the association between clinical features and demyelination, multivariate logistic analysis was also performed. It was shown that hyperuricemia and higher CD8 + T cells were independent risk factors for demyelination in SLE ( p < 0.05). All data were summarized in Table 5 . Table 5 Univariate and multivariate logistic regression analyses of demyelination in SLE patients. NPSLE: systemic lupus erythematosus; LN: lupus nephritis. Univariate analysis Multivariate analysis OR (95% CI ) p -value OR (95% CI ) p -value NPSLE 2.175 (1.313–3.599) 0.002 0.485 (0.096–2.449) 0.381 LN 1.822 (1.105–3.005) 0.019 1.366 (0.791–2.359) 0.263 Hypertension 1.736 (1.008–2.990) 0.047 1.157 (0.610–2.195) 0.654 Hyperuricemia 1.896 (1.037–3.467) 0.038 2.129 (1.313–4.006) 0.019 Arthritis 0.537 (0.325–0.885) 0.015 0.500 (0.295–0.846) 0.010 Polyserous effusions 2.027 (1.068–3.846) 0.031 1.262 (0.605–2.632) 0.535 Cardiac involvement 5.641 (1.116–28.511) 0.036 3.342 (0.601–18.587 0.168 Proteinuria 1.945 (1.178–3.211) 0.009 1.160 (0.601–2.238) 0.658 Albuminuria 1.122 (0.971–1.295) 0.117 1.135 (0.962–1.339) 0.132 CD8 + T cells 1.040 (1.011–1.069) 0.006 1.056 (1.023–1.089) 0.001 CD4 + T cells/CD8 + T cells 0.488 (0.237–1.004) 0.051 0.587 (0.182–1.898) 0.374 Discussion Currently, MRI is the first choice for neuroimaging of SLE and becomes the most important criteria for imaging assessment of NPSLE 17,18 . The cerebral MRI findings of NPSLE is complicated, and according to a recent study, the brain MRI changes can be classified into 6 types, which including demyelinating changes, vascular lesions, inflammation, edema, coexistence of multiple lesions and no abnormalities 19 . Due to the high resolution of cranial MRI, cerebral lesions can be found in patients without clinical neurological symptoms. With the application of MRI, demyelinating diseases can be detected before obvious clinical symptoms appear. Typical manifestations of demyelination on cerebral MRI are visible high signal lesions on T2WI in various forms near the bilateral ventricles. However, there are few relevant studies on the characteristics of demyelination of CNS in SLE patients. Multiple sclerosis (MS) is a typical immune-mediated chronic inflammatory demyelinating disease, and a number of researches have discussed about its MRI performance. The morphologies of WM lesions in MS are ovoid shape and black holes and lesions are more likely to occur in areas of periventricular than in subcortical 12,20,21 . The MRI findings of demyelination in SLE are different from MS. This is the first study to report the MRI characteristics of SLE complicated with demyelination of CNS. The present study described the MRI findings of intracranial demyelination in SLE into three categories. The most prevalent MRI changes was multiple discrete, focal, small patchy or dotted WM lesions in brain. Patchy or elongated periventricular WM lesions were also common demyelinating changes, while subcortical WM lesions had the least incidence. Checa et al. reported the localizations of WM lesions in NPSLE patients were more common in areas of cortical/subcortical junction (fronto-parietal) than in periventricular, while the morphology has not been described 12 . Most of the type A demyelination in our patients were symmetrical and adjacent to the lateral ventricle, which was consistent with the performance of cerebral small vessel disease. In addition, some patients presented with symmetric or asymmetric demyelinating lesions that are not close to the lateral ventricle, as they were rarely seen in other diseases, this may be specific for SLE. Separate type B lesions were very mild, and most patients with type B demyelination were combined with type A and type C. In this case, type B demyelinating lesions were more severe, and the clinical symptoms of the nervous system were also more serious. This type of demyelination was rare in other diseases, and it should be considered as a typical and specific manifestation of SLE demyelination. Except for SLE, Type C lesions could also occur in some small cerebrovascular diseases and it was not easy to distinguish it from imaging alone. Clinical manifestations and cerebrospinal fluid tests must be taken into consideration, and other diseases should be excluded. In the analysis of clinical characteristics, our data showed that patients with demyelination were more likely to develop NPSLE. The most common NPSLE manifestations in demyelinating SLE patients were cerebrovascular disease and seizure disorders, and it is consistent with the previous reports 22,23 . Meanwhile, our study showed an increase of cognitive dysfunction in patients with demyelination. A limited number of researches have attempted to detect the associations between brain MRI findings and cognitive dysfunctions in SLE patients. Kozora et al. have examined WM lesions in 20 SLE patients without overt CNS disease. Patients showed impairment in the domains of attention and learning, and about 40% of these patients presented with WM lesions 24 . Our data demonstrated that the incidence of autonomic neuropathy in demyelinating patients was increased. Currently, there was no literature related to autonomic neuropathy and demyelination in SLE patients. Mario Habek illustrated the interactions between the immune system and the autonomic nervous system, and their impacts on MS. Autonomic dysfunction in MS patients can be confirmed at the clinical and molecular level 25 . Polyneuropathy was the most common peripheral neuropathy in patients with SLE, which was consistent with the previous report 26 . At present, the relationship between CNS demyelination and polyneuropathy in SLE was poorly understood, however, there were many articles on peripheral nerve system (PNS) demyelination in SLE patients. In addition, the results of our study revealed that DS developed in 8.62% (5/58) NPSLE patients with demyelination, and the prevalence of DS in our SLE cohort was 1.8% (5/273). This was higher than 1% that reported previously 15 . The reason for this difference might be that most of the SLE patients enrolled in our study had or were suspected of having neurological symptoms. Our data showed that peripheral neuropathy and CNS involvement increased significantly in SLE patients with central demyelination, compared to those without central demyelination. It suggested that the demyelinating lesions in these patients may affect not only CNS but also PNS. However, it is still necessary to analyze the specific manifestations and examinations of the patient’s nerve involvement furtherly. In analyzing the relationship between demyelination in SLE and complications, our data showed that hypertension and hyperuricemia in patients with demyelination were more common than that without demyelination. Previous study has reported cerebral WM demyelination was associated with hypertension in SLE patients, and our data were consistent with it 27 . The relationship between hyperuricemia and demyelination in SLE has not been reported, but MS-related studies have found that uric acid concentration increased in serum and cerebrospinal fluid of MS patients. Uric acid has been proven to be one of the danger signals involved in NLRP3 inflammasome activation, which is associated with the progression of MS disease 28 . In patients with SLE, the connection between demyelination of CNS and renal impairments has not been discussed. Girolami et al. reported a patient who developed chronic inflammatory demyelinating polyneuropathy (CIDP), heavy proteinuria occurred when neuropathy recurred, and the renal biopsy showed focal segmental glomerulosclerosis (FSGS). The combination of CIDP and FSGS suggested synergistic cellular and humoral autoimmune mechanisms related to either the cross-reaction within antigenic targets or mimicry between neural and renal epitopes 29 . Our study showed that SLE patients with demyelination of CNS was tend to suffer LN. The molecular mechanism of this phenomenon needs to be further explored. Correlation between demyelination of SLE patients and cardiac involvement has not been declared. Mukerji et al. reviewed GBS with cardiovascular complications 30 . The article mentioned that up to 70% of GBS could be observed with autonomic nervous system disorders, which were mainly manifested as sympathetic hyperactivity rather than parasympathetic hypoxia. Pathologically, infiltration of various lymphocytes and macrophage-mediated demyelination could be seen consistent with symptoms. Cardiovascular disorders related to GBS include heart rate variability, blood pressure variability, cardiomyopathy and electrocardiogram changes. However, in our study, cardiac involvement in SLE patients was mainly manifested as lupus cardiomyopathy. Our study displayed higher levels of CD8 + T cells in patients with demyelination. Previous studies have shown that CD8 + T cells played an important role in demyelinating diseases 31–33 . CD4 + T cells usually cause tissue damage indirectly by recruiting and activating myeloid cells, while CD8 + T cells themselves can get damage or death to target cells 32 . CD8 + T cells are all set to contribute to demyelinating lesions and axonal damage. Multiple evidences indicate that CD8 + T lymphocytes play a broader role in MS pathogenesis than previously thought. In active acute and chronic MS brain injury, CD8 + T cells not only predominate over CD4 + T cells, but they also proliferate clonally, and this suggests that they are involved in antigen-driven processes 34,35 . Our study reported for the first time that higher CD8 + T cells was associated with demyelination of CNS in SLE. It is still need to be confirmed whether its immunological mechanism works in the same way as those CD8 + T cells involved in inflammatory demyelinating disease as reported in existing studies, or whether it has its own pathophysiological and immunological mechanisms. In a subgroup analysis of NPSLE patients, we found that patients with demyelination inclined to complicate with hypertension and hyperuricemia, and tend to have polyserous effusions, cardiac involvement, peripheral neuropathy, proteinuria and higher levels of CD8 + T cells. However, NPSLE patients without demyelination were prone to suffer weight loss, arthritis and rash. Our study showed that hyperuricemia and higher CD8 + T cells were independent risk factors for demyelination. It suggested that we should be alert to the possibility of demyelination when dealing with SLE patients with the situation of hyperuricemia or CD8 + T cell increase. In conclusion, our study demonstrated that SLE with demyelination was not rare. We classified the imaging changes of SLE patients complicated with demyelination of CNS, and demonstrated that SLE with demyelination was strongly associated with NPSLE, LN, polyserous effusions and cardiac involvement. Hyperuricemia and higher levels of CD8 + T cells were indicators for demyelination in SLE. Patients with SLE emerged the above conditions should be vigilant to the occurrence of demyelination, and it is conducive to early detection of lesions, so as to make a more comprehensive assessment of the disease. Declarations Acknowledgements This study was supported by grants from the National Natural Science Foundation of China (81771743 to Dr R Li and 81801619 to Dr X Li), Macao Science and Technology Development Fund (0094/2018/A3 to Dr Z Li). Author contributions Qian Guo performed most of the data collection, analysis and drafted the manuscript. Yang He, Xia Liu and Xu-guang Gao participated in MRI interpretation and classification. Zhan-Guo Li and Ru Li conceived the study and participated in the interpretation of results. Jing Xu, Xue Li, Yue Sun and Ya-juan Xiang participated in the data collection. All authors read and approved the final manuscript. Competing interests The authors declare no competing interests. References 1 Piga, M., Vacca, A., Porru, G., Cauli, A. & Mathieu, A. Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis. Clin Exp Rheumatol 28 , 504-510 (2010). 2 Jeltsch-David, H. & Muller, S. Neuropsychiatric systemic lupus erythematosus: pathogenesis and biomarkers. Nat Rev Neurol 10 , 579-596, doi:10.1038/nrneurol.2014.148 (2014). 3 Lauvsnes, M. B. & Omdal, R. Systemic lupus erythematosus, the brain, and anti-NR2 antibodies. J Neurol 259 , 622-629, doi:10.1007/s00415-011-6232-5 (2012). 4 Kozora, E. & Filley, C. M. Cognitive dysfunction and white matter abnormalities in systemic lupus erythematosus. 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Neuropsychol Rev 18 , 149-166, doi:10.1007/s11065-008-9061-2 (2008). 28 Piancone, F. et al. Monosodium Urate Crystals Activate the Inflammasome in Primary Progressive Multiple Sclerosis. Front Immunol 9 , 983, doi:10.3389/fimmu.2018.00983 (2018). 29 Girolami, F., Galassi, G., Furci, L., Ariatti, A. & Cappelli, G. Coincident chronic inflammatory demyelinating polyneuropathy and focal segmental glomerulosclerosis: a common autoimmunity? Clin Exp Nephrol 14 , 294-295, doi:10.1007/s10157-009-0259-2 (2010). 30 Mukerji, S., Aloka, F., Farooq, M. U., Kassab, M. Y. & Abela, G. S. Cardiovascular complications of the Guillain-Barre syndrome. Am J Cardiol 104 , 1452-1455, doi:10.1016/j.amjcard.2009.06.069 (2009). 31 Willing, A. & Friese, M. A. CD8-mediated inflammatory central nervous system disorders. Curr Opin Neurol 25 , 316-321, doi:10.1097/WCO.0b013e328352ea8b (2012). 32 Johnson, T. A., Jirik, F. R. & Fournier, S. 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Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Zhanguo","middleName":"","lastName":"Li","suffix":""}],"badges":[],"createdAt":"2021-07-04 09:29:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-685756/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-685756/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":13703194,"identity":"becbbdd4-25b3-4e1b-a1a2-58be560683ec","added_by":"auto","created_at":"2021-09-17 13:39:45","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":426329,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-685756/v1/d7d058dd-f809-4ca2-b25f-403fc918249d.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eFeatures of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSystemic lupus erythematosus (SLE) is an autoimmune multi-system disease\u0026nbsp;\u003c/p\u003e\n\u003cp\u003echaracterized by complex and varied clinical manifestations\u0026nbsp;\u003csup\u003e1-4\u003c/sup\u003e. Neuropsychiatric manifestations appeared in about 37-90% of patients, including central, peripheral, autonomous nervous system and psychiatric involvement\u0026nbsp;\u003csup\u003e5-7\u003c/sup\u003e, potentially with worse prognosis and mortality\u0026nbsp;\u003csup\u003e8\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eDemyelination is a term to describe a loss of the lipid-rich myelin sheaths with axons preserved relatively. It can not only invade the nervous system as primary demyelinating disorders, but also can be presented as a clinical manifestation of the autoimmune rheumatic disease. In SLE the\u0026nbsp;demyelination of central nervous system (CNS) has been reported in about 0.3\u0026ndash;2.7%\u0026nbsp;\u003csup\u003e9-11\u003c/sup\u003e.\u0026nbsp;Antinuclear antibodies (ANA) can be found in some primary demyelinating diseases, and anti-neuronal antibodies can also be found in SLE patients. The two can be independent of each other or overlap\u0026nbsp;\u003csup\u003e12,13\u003c/sup\u003e.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDemyelinating syndrome\u0026nbsp;is one of the 19 defined syndromes in neuropsychiatric systemic lupus erythematosus (NPSLE)\u0026nbsp;\u003csup\u003e14\u003c/sup\u003e with a prevalence of 1% and has been defined according to the presence of two or more\u0026nbsp;manifestations of demyelinating disease\u0026nbsp;\u003csup\u003e15\u003c/sup\u003e.\u0026nbsp;However, demyelination in SLE patients is atypical and most of them are insufficient for the diagnosis of demyelinating syndrome. Since demyelinating lesions in SLE can be clinically silent and are\u0026nbsp;not pathognomonic, it is not easy to detect the demyelination in the early stage. Meanwhile, treatment for demyelinating disease is also a clinical dilemma. There are few reports to analyze characteristics of demyelinating lesions of CNS\u0026nbsp;in SLE patients. The aim of this study was to explore the clinical features and cerebral\u0026nbsp;magnetic resonance imaging\u0026nbsp;(MRI) changes of patients with SLE\u0026nbsp;complicated with\u0026nbsp;demyelination of CNS.\u003c/p\u003e\n"},{"header":"Methods","content":" \u003cp\u003e\u003cb\u003eStudy population.\u003c/b\u003e This retrospective monocentric study collected data from a consecutive cohort of 1191 patients with SLE who were hospitalized in the Department of Rheumatology and Immunology, Peking University People\u0026rsquo;s Hospital from July 2016 to January 2020. The diagnosis of SLE was based on 1997 revised American College of Rheumatology (ACR) classification criteria \u003csup\u003e16\u003c/sup\u003e. Of these patients, 273 underwent cerebral MRI owing to various reasons. Patients were divided into two groups: patients with and without demyelination which was determined by rheumatologist, neurologist and radiologist. All participants provided written informed consent (informed consent for participants\u0026thinsp;\u0026lt;\u0026thinsp;18 years of age was obtained from a parent and/or legal guardian), in accordance with the Declaration of Helsinki. The research protocol was approved by the Institutional Research Ethics Committee of the Peking University People's Hospital (2019PHB007-01).\u003c/p\u003e \u003cp\u003e \u003cb\u003eCerebral MRI scans.\u003c/b\u003e Cerebral MRI scans were performed on GE Signa HDxt 3.0 Tesla MRI scanner equipped with an 8-channel receive head coil and gradient coil field strength of 40mT/m. After three-plane positioning, sagittal T1-weighted images (WI) scan was performed, the front and back connections were used as the scan baseline, axial scan consisted of T1WI (TR/TE\u0026thinsp;=\u0026thinsp;2390/10.688ms, FOV\u0026thinsp;=\u0026thinsp;24cm, matrix 384\u0026times;286), T2WI (TR/TE\u0026thinsp;=\u0026thinsp;5200/107.408ms, matrix 320\u0026times;320), T2WI-FLAIR (TR/TE\u0026thinsp;=\u0026thinsp;7902/140.452ms, matrix 288\u0026times;224). The scanning range was from the top of the skull to the foramen magnum, with a thickness of 5 mm and an interval of 1.5 mm. Diffusion-weighted imaging (DWI) used single-shot spin echo- planar imaging (TR/ TE\u0026thinsp;=\u0026thinsp;5400/90.3ms, FOV\u0026thinsp;=\u0026thinsp;24cm, matrix 128\u0026times;128, NEX\u0026thinsp;=\u0026thinsp;1), with copying the scan plane of axis sequence. Definition of cerebral MRI demyelinating lesions was: patchy or elongated T1-WI hypointense and T2-WI hyperintense lesions in periventricular white matter (WM), focal and patchy subcortical T1-WI hypointense and T2-WI hyperintense WM lesions, and/or multiple discrete, focal, small patchy or dotted cerebral T1-WI hypointense and T2-WI hyperintense WM lesions in brain, with no peripheral edema and space-occupying effect, except age, endocrine, nutritional and metabolic, hereditary or other interpretable diseases caused by small vessel disease. The MRI findings of the demyelination in SLE were divided into three categories: type A. patchy or elongated periventricular white matter (WM) lesions; type B. focal and patchy subcortical WM lesions; type C. multiple discrete, focal, small patchy or dotted WM lesions in brain.\u003c/p\u003e \u003cp\u003e \u003cb\u003eClinical and laboratory assessment.\u003c/b\u003e General characteristics of patients were collected, including demographic data, disease duration, age at onset of symptoms, coexistence of other immune diseases, family history of immune disease, smoking history and drinking history. Complications included hypertension, diabetes, coronary heart disease, hyperlipidemia, hyperuricemia or cerebrovascular disease. NPSLE diagnosis was made according to the 1999 ACR case definitions for NPSLE syndromes (including central nervous involvement and peripheral neuropathy) \u003csup\u003e14\u003c/sup\u003e. Lupus nephritis (LN) was defined by the following criteria: a) persistent proteinuria greater than 0.5g per day, or b) the presence of granular, red cell, hemoglobin, tubular, or mixed casts. Hematological involvement was defined as white blood cell or platelet lower than normal value and autoimmune hemolytic anemia. Lung involvement contained interstitial lung disease, alveolar hemorrhage, pulmonary hypertension and others related with SLE. Digestive system involvement including intestinal pseudo-obstruction, protein-losing enteropathy, gastrointestinal bleeding, liver injury, pancreatitis and others due to SLE. Cardiac involvement was defined as cardiac manifestations related with SLE, including cardiomyopathy, heart valvular disease and others. Other clinical manifestations including fever (noninfectious fever), weight loss (weight loss༞5% within 1 month), arthritis, rash, photosensitivity, alopecia, aphthous ulcer, Raynaud phenomenon, myositis, pleuritis, pericarditis, polyserous effusions and retinopathy were recorded. Laboratory data included complete blood cell count, ANA, anti-double stranded DNA (ds-DNA) antibodies, anti-Sm antibodies, anti-SSA antibodies, anti-SSB antibodies, anti-RNP antibodies, anti-membrane DNA (mDNA) antibodies, anti-ribosomal Po (Rib-Po) antibodies, anti-nucleosome antibodies (ANUA), anti-β2 glicoprotein-I (β2-GPI) antibodies, anti-cardiolipin (aCL) antibodies, lupus anticoagulant (LA), Coomb\u0026rsquo;s test, rheumatoid factor (RF), proteinuria and levels of albuminuria, creatinine, erythrocyte sedimentation rate (ESR), IgG, IgA, IgM, complement 3 (C3), complement 4 (C4), total T cells percent, CD4\u003csup\u003e+\u003c/sup\u003e T cells percent, CD8\u003csup\u003e+\u003c/sup\u003eT cell percent and CD4\u003csup\u003e+\u003c/sup\u003eT cells/CD8\u003csup\u003e+\u003c/sup\u003e T cells.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis.\u003c/b\u003e The Statistical Package for Social Sciences version23.0 (SPSS, Chicago, IL, USA) was performed to analyze the data. Continuous variables were presented as mean and standard deviation (SD) or median and interquartile range (IQR). Category data were presented as percentages. Differences between groups of continuous variables are analyzed by independent student\u0026rsquo;s t-test or non-parametric Wilcoxon Test. For categorical variables, Chi-squared test or non-parametric Fisher\u0026rsquo;s exact test were used to compare frequencies in different groups. Association between different clinical/laboratory variables and demyelination was studied using univariate and multivariate logistic regression models, the association measurement was shown as odds ratios (ORs) calculation, with its 95% confidence intervals (CI 95%). \u003cem\u003ep\u003c/em\u003e value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was regarded as statistically significant.\u003c/p\u003e "},{"header":"Results","content":" \u003cp\u003e \u003cb\u003ePatients demographic characteristics.\u003c/b\u003e Of these 273 patients who underwent cerebral MRI, 91.2% were women, with a mean age of 38.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.8 years and a median disease course of 5.0 (1.0, 13.0) years. The median age at onset of symptoms was 27 (21, 39) years.\u003c/p\u003e \u003cp\u003e \u003cb\u003eMRI findings of the demyelination in SLE.\u003c/b\u003e Among the 273 SLE patients with MRI, 98 had demyelinating changes, with 5 of them eligible for demyelinating syndrome (DS). Other patients have SLE-related demyelinating changes, but not DS. Of all the patients with demyelination, the incidences of type A, B and C were 54.1% (53/98), 11.2% (11/98) and 92.9% (91/98), respectively. Fifty-one percent of the patients were with overlap of 2 or 3 types and type C was the most common subgroup combined with other types. (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Type C and type A\u0026thinsp;+\u0026thinsp;C account for the majority of patients. Compared with those who performed as type C alone, patients with type A\u0026thinsp;+\u0026thinsp;C were tend to develop hypertension and peripheral neuropathy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, respectively), and had longer disease duration and older age at onset of symptoms (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, respectively).\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\u003eMRI findings of the demyelination in SLE.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSLE with demyelination (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cb\u003en\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cb\u003e%\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u0026thinsp;+\u0026thinsp;B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u0026thinsp;+\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eB\u0026thinsp;+\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eA\u0026thinsp;+\u0026thinsp;B\u0026thinsp;+\u0026thinsp;C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.1\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 \u003cb\u003eClinical characteristics of SLE patients with demyelination.\u003c/b\u003e The clinical characteristics of patients with SLE were showed in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Compared with those without demyelination, the patients with demyelination were more likely to develop NPSLE (including peripheral neuropathy and central nervous involvement) and LN (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05, respectively). The types of NPSLE prone to occur in patients with demyelination included cerebrovascular disease, demyelinating syndrome, seizure disorders, cognitive dysfunction, autonomic disorder and polyneuropathy. Hypertension and hyperuricemia were the common complications (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Patients with demyelination tend to have polyserous effusions and cardiac involvement (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\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 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical characteristics of patients with SLE in different groups. NPSLE: systemic lupus erythematosus; LN: lupus nephritis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSLE with demyelination (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSLE without demyelination (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneral characteristics\u003c/b\u003e\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, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90 (91.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e159 (90.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.784\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, median (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.0 (29.0,51.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.5 (22.0,52.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisease duration, median (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6.0 (2.0,14.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0 (0.7,10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.207\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset of symptoms, median (IQR), years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.0 (23.0,40.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23.9 (19.0,39.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.142\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoexistence of other immune diseases, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (32.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of immune disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (8.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.474\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoking history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDrinking history, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.704\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComplications\u003c/b\u003e\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\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (8.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.568\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoronary heart disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (34.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.143\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperuricemia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (26.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCerebrovascular disease, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.244\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical manifestations\u003c/b\u003e\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\u003eNPSLE, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e58 (59.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70 (40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral neuropathy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCentral nervous involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e53 (54.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64 (36.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLN, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52(53.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (38.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.018\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.656\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDigestive system involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (10.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17 (9.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.897\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e85 (86.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137 (78.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFever, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e57 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e108 (61.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.565\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight loss, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19 (19.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39 (22.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.574\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthritis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e102 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55 (56.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e114 (65.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.141\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhotosensitivity, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51 (29.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.938\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlopecia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e48 (49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e90 (51.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.698\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAphthous ulcer, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.823\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRaynaud phenomenon, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.681\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMyositis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (2.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.497\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePleuritis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePericarditis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.538\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyserous effusions, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (23.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.029\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetinopathy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.500\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 \u003cb\u003eComparison of laboratory findings of SLE patients with demyelination.\u003c/b\u003e In laboratory analysis, the patients with demyelination had higher frequency of proteinuria (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In addition, higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells were found in patients with demyelination (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). There were less autoantibodies to ds-DNA, Sm and Rib-Po in the demyelination group, while was not significant statistically (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\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 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eLaboratory findings of patients with SLE in different groups. ANA: antinuclear antibodies; Anti-dsDNA: anti-double stranded DNA antibodies; Anti-Sm: anti-Sm antibodies; Anti-SSA: anti-SSA antibodies; Anti-SSB: anti-SSB antibodies; Anti-RNP: anti-RNP antibodies; Anti-mDNA: anti-membrane DNA antibodies; Rib-Po: anti-ribosomal Po antibodies; ANUA: anti-nucleosome antibodies; β2-GPI: anti-β2 glicoprotein-I antibodies; aCL: anti-cardiolipin antibodies; LA: lupus anticoagulant; RF: rheumatoid factor; ESR: erythrocyte sedimentation rate; C3: complement 3; C4: complement 4.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSLE with demyelination (n\u0026thinsp;=\u0026thinsp;98)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSLE without demyelination (n\u0026thinsp;=\u0026thinsp;175)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e91 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e170 (97.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-dsDNA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e54 (55.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e105 (60.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.431\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-Sm, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e14 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e40 (22.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.088\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-SSA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e56 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e100 (57.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.000\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-SSB, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (15.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e19 (10.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.286\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-RNP, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e36 (36.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e75 (42.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnti-mDNA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (5.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (6.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.690\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRib-Po, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (12.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANUA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e48 (49.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e85 (48.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.948\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eβ2-GPI, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (22.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e31 (17.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.343\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eaCL, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e38 (21.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.277\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLA, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e29 (29.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e37 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCoomb\u0026rsquo;s test, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59 (60.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e95 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRF, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e25 (25.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e41 (23.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.700\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53 (54.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e66 (37.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbuminuria, median (IQR), g/day\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.360 (0.130,1.320)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.185 (0.080,0.778)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine, median (IQR),\u0026micro;mol/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e58 (49.0,84.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e54 (46.5,65.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eESR, median (IQR), mm/h\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e27.0 (11.0,63.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e28 (11.0,53.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.091\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgG, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15.952\u0026thinsp;\u0026plusmn;\u0026thinsp;9.830\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e15.873\u0026thinsp;\u0026plusmn;\u0026thinsp;7.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.944\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgA, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.757\u0026thinsp;\u0026plusmn;\u0026thinsp;2.897\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e2.609\u0026thinsp;\u0026plusmn;\u0026thinsp;1.273\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.636\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIgM, median (IQR), g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.838 (0.42,1.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1.030 (0.677,1.485)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.111\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC3, median (IQR), g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.625 (0.372,0.706)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.504 (0.346,0.726)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.851\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eC4, median (IQR), g/L\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.126 (0.074,0.156)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.107 (0.568,0.146)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.691\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal T cells, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e72.72\u0026thinsp;\u0026plusmn;\u0026thinsp;14.46\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e70.43\u0026thinsp;\u0026plusmn;\u0026thinsp;14.50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.345\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003eT cells, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30.00\u0026thinsp;\u0026plusmn;\u0026thinsp;9.83\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e33.01\u0026thinsp;\u0026plusmn;\u0026thinsp;11.34\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8\u003csup\u003e+\u003c/sup\u003eTcells, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e40.69\u0026thinsp;\u0026plusmn;\u0026thinsp;13.60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34.97\u0026thinsp;\u0026plusmn;\u0026thinsp;11.10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003eT cells /CD8\u003csup\u003e+\u003c/sup\u003eT cells,\u003c/p\u003e \u003cp\u003emedian (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.67 (0.51,0.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.94 (0.68,1,28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\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 \u003cb\u003eComparison of NPSLE patients with and without demyelination.\u003c/b\u003e In further analysis of the patients with NPSLE, those with demyelination were more likely to complicated with hypertension and hyperuricemia, and tend to have polyserous effusions, cardiac involvement, peripheral neuropathy, proteinuria and higher CD8\u003csup\u003e+\u003c/sup\u003e T cells (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\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 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of NPSLE patients with and without demyelination. LN: lupus nephritis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSLE with demyelination (n\u0026thinsp;=\u0026thinsp;58)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSLE without demyelination (n\u0026thinsp;=\u0026thinsp;70)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLN, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e34 (58.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (41.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.053\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.008\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperuricemia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e15 (25.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (31.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.489\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight loss, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e10 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (32.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthritis, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e22 (37.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e46 (65.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRash, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (51.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53 (75.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.005\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyserous effusions, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (27.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac involvement, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (6.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.040\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePeripheral neuropathy, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21 (36.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (18.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.025\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e38 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8\u003csup\u003e+\u003c/sup\u003eT cells, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD, %\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e43.619\u0026thinsp;\u0026plusmn;\u0026thinsp;13.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34.105\u0026thinsp;\u0026plusmn;\u0026thinsp;10.825\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.001\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 \u003cb\u003eRisk factors for demyelination in SLE patients.\u003c/b\u003e Univariate analysis suggested that SLE patients who had NPSLE, LN, hypertension, hyperuricemia, polyserous effusions, cardiac involvement, proteinuria and higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells were more likely to progress demyelination in brains (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). To further investigate the association between clinical features and demyelination, multivariate logistic analysis was also performed. It was shown that hyperuricemia and higher CD8\u003csup\u003e+\u003c/sup\u003e T cells were independent risk factors for demyelination in SLE (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). All data were summarized in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eUnivariate and multivariate logistic regression analyses of demyelination in SLE patients. NPSLE: systemic lupus erythematosus; LN: lupus nephritis.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eUnivariate analysis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eMultivariate analysis\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eOR\u003c/span\u003e \u003cb\u003e(95%\u003c/b\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eCI\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003cb\u003e-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eOR\u003c/span\u003e \u003cb\u003e(95%\u003c/b\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003eCI\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cspan type=\"BoldItalic\" class=\"BoldItalic\" name=\"Emphasis\"\u003ep\u003c/span\u003e\u003cb\u003e-value\u003c/b\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNPSLE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.175 (1.313\u0026ndash;3.599)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.002\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.485 (0.096\u0026ndash;2.449)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.381\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.822 (1.105\u0026ndash;3.005)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.366 (0.791\u0026ndash;2.359)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.263\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.736 (1.008\u0026ndash;2.990)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.047\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.157 (0.610\u0026ndash;2.195)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.654\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperuricemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.896 (1.037\u0026ndash;3.467)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.038\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.129 (1.313\u0026ndash;4.006)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.019\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.537 (0.325\u0026ndash;0.885)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.500 (0.295\u0026ndash;0.846)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePolyserous effusions\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.027 (1.068\u0026ndash;3.846)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.031\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.262 (0.605\u0026ndash;2.632)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.535\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiac involvement\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5.641 (1.116\u0026ndash;28.511)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.342 (0.601\u0026ndash;18.587\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.168\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProteinuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.945 (1.178\u0026ndash;3.211)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.160 (0.601\u0026ndash;2.238)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.658\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbuminuria\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.122 (0.971\u0026ndash;1.295)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.117\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.135 (0.962\u0026ndash;1.339)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.132\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD8\u003csup\u003e+\u003c/sup\u003eT cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.040 (1.011\u0026ndash;1.069)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.056 (1.023\u0026ndash;1.089)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCD4\u003csup\u003e+\u003c/sup\u003eT cells/CD8\u003csup\u003e+\u003c/sup\u003eT cells\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.488 (0.237\u0026ndash;1.004)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.587 (0.182\u0026ndash;1.898)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.374\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e "},{"header":"Discussion","content":" \u003cp\u003eCurrently, MRI is the first choice for neuroimaging of SLE and becomes the most important criteria for imaging assessment of NPSLE \u003csup\u003e17,18\u003c/sup\u003e. The cerebral MRI findings of NPSLE is complicated, and according to a recent study, the brain MRI changes can be classified into 6 types, which including demyelinating changes, vascular lesions, inflammation, edema, coexistence of multiple lesions and no abnormalities \u003csup\u003e19\u003c/sup\u003e. Due to the high resolution of cranial MRI, cerebral lesions can be found in patients without clinical neurological symptoms. With the application of MRI, demyelinating diseases can be detected before obvious clinical symptoms appear. Typical manifestations of demyelination on cerebral MRI are visible high signal lesions on T2WI in various forms near the bilateral ventricles. However, there are few relevant studies on the characteristics of demyelination of CNS in SLE patients. Multiple sclerosis (MS) is a typical immune-mediated chronic inflammatory demyelinating disease, and a number of researches have discussed about its MRI performance. The morphologies of WM lesions in MS are ovoid shape and black holes and lesions are more likely to occur in areas of periventricular than in subcortical \u003csup\u003e12,20,21\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe MRI findings of demyelination in SLE are different from MS. This is the first study to report the MRI characteristics of SLE complicated with demyelination of CNS. The present study described the MRI findings of intracranial demyelination in SLE into three categories. The most prevalent MRI changes was multiple discrete, focal, small patchy or dotted WM lesions in brain. Patchy or elongated periventricular WM lesions were also common demyelinating changes, while subcortical WM lesions had the least incidence. Checa et al. reported the localizations of WM lesions in NPSLE patients were more common in areas of cortical/subcortical junction (fronto-parietal) than in periventricular, while the morphology has not been described \u003csup\u003e12\u003c/sup\u003e. Most of the type A demyelination in our patients were symmetrical and adjacent to the lateral ventricle, which was consistent with the performance of cerebral small vessel disease. In addition, some patients presented with symmetric or asymmetric demyelinating lesions that are not close to the lateral ventricle, as they were rarely seen in other diseases, this may be specific for SLE. Separate type B lesions were very mild, and most patients with type B demyelination were combined with type A and type C. In this case, type B demyelinating lesions were more severe, and the clinical symptoms of the nervous system were also more serious. This type of demyelination was rare in other diseases, and it should be considered as a typical and specific manifestation of SLE demyelination. Except for SLE, Type C lesions could also occur in some small cerebrovascular diseases and it was not easy to distinguish it from imaging alone. Clinical manifestations and cerebrospinal fluid tests must be taken into consideration, and other diseases should be excluded.\u003c/p\u003e \u003cp\u003eIn the analysis of clinical characteristics, our data showed that patients with demyelination were more likely to develop NPSLE. The most common NPSLE manifestations in demyelinating SLE patients were cerebrovascular disease and seizure disorders, and it is consistent with the previous reports \u003csup\u003e22,23\u003c/sup\u003e. Meanwhile, our study showed an increase of cognitive dysfunction in patients with demyelination. A limited number of researches have attempted to detect the associations between brain MRI findings and cognitive dysfunctions in SLE patients. Kozora et al. have examined WM lesions in 20 SLE patients without overt CNS disease. Patients showed impairment in the domains of attention and learning, and about 40% of these patients presented with WM lesions \u003csup\u003e24\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eOur data demonstrated that the incidence of autonomic neuropathy in demyelinating patients was increased. Currently, there was no literature related to autonomic neuropathy and demyelination in SLE patients. Mario Habek illustrated the interactions between the immune system and the autonomic nervous system, and their impacts on MS. Autonomic dysfunction in MS patients can be confirmed at the clinical and molecular level \u003csup\u003e25\u003c/sup\u003e. Polyneuropathy was the most common peripheral neuropathy in patients with SLE, which was consistent with the previous report \u003csup\u003e26\u003c/sup\u003e. At present, the relationship between CNS demyelination and polyneuropathy in SLE was poorly understood, however, there were many articles on peripheral nerve system (PNS) demyelination in SLE patients. In addition, the results of our study revealed that DS developed in 8.62% (5/58) NPSLE patients with demyelination, and the prevalence of DS in our SLE cohort was 1.8% (5/273). This was higher than 1% that reported previously \u003csup\u003e15\u003c/sup\u003e. The reason for this difference might be that most of the SLE patients enrolled in our study had or were suspected of having neurological symptoms. Our data showed that peripheral neuropathy and CNS involvement increased significantly in SLE patients with central demyelination, compared to those without central demyelination. It suggested that the demyelinating lesions in these patients may affect not only CNS but also PNS. However, it is still necessary to analyze the specific manifestations and examinations of the patient\u0026rsquo;s nerve involvement furtherly.\u003c/p\u003e \u003cp\u003eIn analyzing the relationship between demyelination in SLE and complications, our data showed that hypertension and hyperuricemia in patients with demyelination were more common than that without demyelination. Previous study has reported cerebral WM demyelination was associated with hypertension in SLE patients, and our data were consistent with it \u003csup\u003e27\u003c/sup\u003e. The relationship between hyperuricemia and demyelination in SLE has not been reported, but MS-related studies have found that uric acid concentration increased in serum and cerebrospinal fluid of MS patients. Uric acid has been proven to be one of the danger signals involved in NLRP3 inflammasome activation, which is associated with the progression of MS disease \u003csup\u003e28\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn patients with SLE, the connection between demyelination of CNS and renal impairments has not been discussed. Girolami et al. reported a patient who developed chronic inflammatory demyelinating polyneuropathy (CIDP), heavy proteinuria occurred when neuropathy recurred, and the renal biopsy showed focal segmental glomerulosclerosis (FSGS). The combination of CIDP and FSGS suggested synergistic cellular and humoral autoimmune mechanisms related to either the cross-reaction within antigenic targets or mimicry between neural and renal epitopes \u003csup\u003e29\u003c/sup\u003e. Our study showed that SLE patients with demyelination of CNS was tend to suffer LN. The molecular mechanism of this phenomenon needs to be further explored.\u003c/p\u003e \u003cp\u003eCorrelation between demyelination of SLE patients and cardiac involvement has not been declared. Mukerji et al. reviewed GBS with cardiovascular complications \u003csup\u003e30\u003c/sup\u003e. The article mentioned that up to 70% of GBS could be observed with autonomic nervous system disorders, which were mainly manifested as sympathetic hyperactivity rather than parasympathetic hypoxia. Pathologically, infiltration of various lymphocytes and macrophage-mediated demyelination could be seen consistent with symptoms. Cardiovascular disorders related to GBS include heart rate variability, blood pressure variability, cardiomyopathy and electrocardiogram changes. However, in our study, cardiac involvement in SLE patients was mainly manifested as lupus cardiomyopathy.\u003c/p\u003e \u003cp\u003eOur study displayed higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells in patients with demyelination. Previous studies have shown that CD8\u003csup\u003e+\u003c/sup\u003e T cells played an important role in demyelinating diseases \u003csup\u003e31\u0026ndash;33\u003c/sup\u003e. CD4\u003csup\u003e+\u003c/sup\u003e T cells usually cause tissue damage indirectly by recruiting and activating myeloid cells, while CD8\u003csup\u003e+\u003c/sup\u003e T cells themselves can get damage or death to target cells \u003csup\u003e32\u003c/sup\u003e. CD8\u003csup\u003e+\u003c/sup\u003e T cells are all set to contribute to demyelinating lesions and axonal damage. Multiple evidences indicate that CD8\u003csup\u003e+\u003c/sup\u003e T lymphocytes play a broader role in MS pathogenesis than previously thought. In active acute and chronic MS brain injury, CD8\u003csup\u003e+\u003c/sup\u003e T cells not only predominate over CD4\u003csup\u003e+\u003c/sup\u003e T cells, but they also proliferate clonally, and this suggests that they are involved in antigen-driven processes \u003csup\u003e34,35\u003c/sup\u003e. Our study reported for the first time that higher CD8\u003csup\u003e+\u003c/sup\u003e T cells was associated with demyelination of CNS in SLE. It is still need to be confirmed whether its immunological mechanism works in the same way as those CD8\u003csup\u003e+\u003c/sup\u003e T cells involved in inflammatory demyelinating disease as reported in existing studies, or whether it has its own pathophysiological and immunological mechanisms.\u003c/p\u003e \u003cp\u003eIn a subgroup analysis of NPSLE patients, we found that patients with demyelination inclined to complicate with hypertension and hyperuricemia, and tend to have polyserous effusions, cardiac involvement, peripheral neuropathy, proteinuria and higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells. However, NPSLE patients without demyelination were prone to suffer weight loss, arthritis and rash.\u003c/p\u003e \u003cp\u003eOur study showed that hyperuricemia and higher CD8\u003csup\u003e+\u003c/sup\u003e T cells were independent risk factors for demyelination. It suggested that we should be alert to the possibility of demyelination when dealing with SLE patients with the situation of hyperuricemia or CD8\u003csup\u003e+\u003c/sup\u003e T cell increase.\u003c/p\u003e \u003cp\u003eIn conclusion, our study demonstrated that SLE with demyelination was not rare. We classified the imaging changes of SLE patients complicated with demyelination of CNS, and demonstrated that SLE with demyelination was strongly associated with NPSLE, LN, polyserous effusions and cardiac involvement. Hyperuricemia and higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells were indicators for demyelination in SLE. Patients with SLE emerged the above conditions should be vigilant to the occurrence of demyelination, and it is conducive to early detection of lesions, so as to make a more comprehensive assessment of the disease.\u003c/p\u003e "},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was supported by grants from the National Natural Science Foundation of China (81771743 to Dr R Li and 81801619 to Dr X Li),\u0026nbsp;Macao Science and Technology Development Fund (0094/2018/A3 to Dr Z Li).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQian Guo performed most of the data collection, analysis and drafted the manuscript. Yang He, Xia Liu and Xu-guang Gao participated in MRI interpretation and classification. Zhan-Guo Li and Ru Li conceived the study and participated in the interpretation of results. Jing Xu, Xue Li, Yue Sun and Ya-juan Xiang participated in the data collection. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n"},{"header":"References","content":"\u003cp\u003e1\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Piga, M., Vacca, A., Porru, G., Cauli, A. \u0026amp; Mathieu, A. Liver involvement in systemic lupus erythematosus: incidence, clinical course and outcome of lupus hepatitis. \u003cem\u003eClin Exp Rheumatol\u003c/em\u003e \u003cstrong\u003e28\u003c/strong\u003e, 504-510 (2010).\u003c/p\u003e\n\u003cp\u003e2\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Jeltsch-David, H. \u0026amp; Muller, S. 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Based on a consecutive cohort of 1191 SLE patients, 273 patients with cerebral MRI were enrolled to assess cerebral demyelination. Patients were divided into two groups, ie. complicated with or without demyelination. The MRI findings of the cerebral demyelination were divided into three categories: type A, periventricular white matter (WM) lesions; type B, subcortical WM lesions; type C, multiple discrete WM lesions. Among the 273 SLE patients with cerebral MRI, 35.9% (98/273) had demyelinating changes. The incidences of type A, B and C were 54.1% (53/98), 11.2% (11/98) and 92.9% (91/98), respectively. Fifty-one percent of the patients were with overlap of 2 or 3 types. Type C was the most common subgroup combined with other types. Compared with those without demyelination, the patients with demyelination were more likely to develop neuropsychiatric systemic lupus erythematosus (NPSLE), lupus nephritis (LN), hypertension and hyperuricemia (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). Significantly higher rates of polyserous effusions and cardiac involvement were found in the patients with demyelination (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). In addition, the patients with demyelination had higher frequency of proteinuria and higher levels of CD8\u003csup\u003e+\u003c/sup\u003e T cells (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). In multivariate logistic analysis, hyperuricemia and higher CD8\u003csup\u003e+\u003c/sup\u003e T cells were significantly correlated with demyelination in SLE patients (\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.05). The data suggest that demyelination is a common complication in SLE patients and strongly associated with systemic involvements, including NPSLE, LN, polyserous effusions and cardiac involvement. Hyperuricemia and higher CD8\u003csup\u003e+\u003c/sup\u003e T cells were independent risk factors for demyelination in SLE.\u003c/p\u003e","manuscriptTitle":"Features of Cerebral Demyelination and Clinical Relevance in Systemic Lupus Erythematosus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-07-09 16:26:59","doi":"10.21203/rs.3.rs-685756/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":"b385d372-8321-450e-9d60-899649cb9f06","owner":[],"postedDate":"July 9th, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":5530363,"name":"Health Economics \u0026 Outcomes Research"},{"id":5530364,"name":"Rheumatology"},{"id":5530365,"name":"Health Policy"}],"tags":[],"updatedAt":"2021-07-27T06:59:09+00:00","versionOfRecord":[],"versionCreatedAt":"2021-07-09 16:26:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-685756","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-685756","identity":"rs-685756","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}