Correlation between anti-retinal antibodies and lupus retinopathy in systemic lupus erythematosus

Correlation between anti-retinal antibodies and lupus retinopathy 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 Article Correlation between anti-retinal antibodies and lupus retinopathy in systemic lupus erythematosus Qingyi Zou, Linqi Zhang, Yu Cao, Bohao Wang, Muzi Li, Xuewu Zhang, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7950771/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 13 Mar, 2026 Read the published version in Scientific Reports → Version 1 posted 14 You are reading this latest preprint version Abstract Lupus retinopathy (LR) is one of the most frequent and serious complications of Systemic lupus erythematosus (SLE), because it may cause irreversible visual impairment. The aim of this study was to evaluate the association between serum anti-retinal antibodies levels of SLE patients and the incidence of LR. Levels of serum anti-α-enolase antibody (Ab), anti-arrestin Ab, anti-recoverin Ab and anti-IRBP3 Ab were detected in 89 SLE patients (further divided into LR group and non-LR group) and 81 healthy controls by enzyme-linked immunosorbent assay (ELISA). The correlation between these four anti-retinal Ab, SLE activity and the incidence of LR was evaluated by correlation analysis. LR group had a higher SLE disease activity index (SLEDAI, 18 (7) versus 9 (5), P < 0.001), higher frequency of pleurisy (40% versus 20.4%, P = 0.044) and lower level of hemoglobin (102.343 ± 23.157 versus 112.759 ± 19.678, P = 0.025) comparing to non-LR group. LR group had higher levels of anti-α-enolase than non-LR group (P = 0.033) and control group (P < 0.0001). The levels of anti-recoverin in LR group was higher than non-LR group (P = 0.036) and control group (P < 0.0001), while the difference was not significant between non-LR group and control group (P = 0.109). Combination of anti-α-enolase Ab and anti-recoverin Ab for evaluating the incidence of LR in SLE patients had better effectiveness (area under the receiver operating characteristic curve (AUC): 72.68%) compared with only anti-α-enolase Ab (AUC: 65.65%) or anti-recoverin (AUC: 61.96%). Our results suggested that Anti-α-enolase and anti-recoverin may be used as potential biomarkers of lupus retinopathy in SLE patients. Health sciences/Biomarkers Health sciences/Diseases Biological sciences/Immunology Health sciences/Medical research Health sciences/Rheumatology Systemic lupus erythematosus lupus retinopathy anti-α-enolase antibody anti-arrestin antibody anti-recoverin antibody anti-IRBP3 antibody Figures Figure 1 Figure 2 Introduction Systemic lupus erythematosus (SLE) is a chronic connective tissue disease with a wide range of clinical manifestations, characterized by production of autoantibodies directed against nuclear and cytoplasmic antigens which can affect various organs and systems. 1 Lupus retinopathy (LR) is one of the most frequent and serious complications of SLE, which may cause irreversible visual impairment. 2 – 9 Early diagnosis of LR can be helpful to predict and prevent severe visual impairment. Therefore, development of optimal diagnostic biomarker for LR in SLE patients is highly necessary. Recoverin is a calcium-binding protein (molecular weight 23kDa), which inhibits the activity of rhodopsin kinase and regulates the phosphorylation of rhodopsin. It exists in the inner segment and nucleus of photoreceptors and the outer plexiform layer of retina. 10 Anti-recoverin Ab can activated Caspase-9 and Caspase-3 dependent apoptotic pathways by inducing calcium ion influx and cause apoptosis of retinal photoreceptors. 11 – 14 Previous studies have reported that anti-retinal antibodies (ARAs) are associated with autoimmune retinopathy (AIR), 15–18 diabetic retinopathy, 19 central serous chorioretinopathy, 20 macular telangiectasia type 2 21 and some genetic retinopathies such as retinopigmentosa, while the mechanisms of the induction of ARAs and their correlation with LR remained unknown. Alpha-enolase (ENO1) is a subtype of enolase, which has a molecular weight of 46kDa, and catalyzed the production of ATP during glycolysis. It is widely expressed in vascular endothelial cells, cone outer segments, Müller cells and the ganglion cell layer of the retina. 22 ENO1 is closely related to inflammation, autoimmune response, tumor and mitochondria function. Anti-α-enolase plays a pathogenic role by generating immune complexes, increasing intracellular calcium ion concentration and initiating apoptosis. 23 – 25 Arrestin-1 (also named S antigen) is a soluble cytoplasmic protein (molecular weight 48kDa) which is specifically expressed in the photoreceptors. It plays an important role in signal regulation viva binding to G protein-coupled receptors, membrane receptors and a variety of intracellular soluble proteins. 26 Anti-arrestin Ab is involved in the conversion of light and dark adaptation by simple diffusion. 27 , 28 IRBP3 is a sugar lipoprotein about 143kDa, which is the main soluble protein in the photoreceptor matrix. It is secreted by photoreceptor cells, and its main physiological role is to regulate the function of cones, rods, Müller cells and retinal pigment epithelium, 29 and provide retinol and retinoic acid to the retina. In addition, the protein protects the unstable molecules from oxidation and isomerization. 30 Adequate amounts of IRBP3 are therefore essential for the structural and functional integrity of the retina, especially photoreceptor cells. Currently, IRBP is considered to be involved in autoimmune uveitis and is one of the antigens of spontaneous uveitis in humans and animals. 29 , 31 , 32 The aim of this study was to evaluate the association between these four ARAs levels and the incidence of LR in SLE patients. Results Characteristics of participants There are 34 SLE patients in LR group, 55 SLE patients in non-LR group and 81 patients as controls enrolled in this study. Their clinical characteristics are shown in Table 1 . The median age of LR group, non-LR group and control group was 44.5(29), 34(23) and 58(47) respectively. The median age in control group was significant older than in non-LR group (P = 0.026). The proportion of female subjects were significant lower in control group (56/81, 69.1%) than in LR group (27/34, 79.4%) and non-LR group (49/55, 89.1%) (P = 0.022, by Chi-square test) (Table 1 ). The median SLE duration of LR group and non- LR group was 10.5 years and 6 years, ranging from 20 days to 50 years and 6 months to 42 years respectively. Table 1 Characteristics of participants Item LR group (n = 34) non-LR group (n = 55) control group (n = 81) P value Age/year, M(IQR) 44.5 (29) 34 (23) 58 (47) 0.031* Age range 18ཞ73 17ཞ81 17ཞ87 Gender, n (%) Male 7 (20.60) 6 (10.90) 25 (30.9) 0.022* Female 27 (79.40) 49 (89.1) 56 (69.1) SLE duration/year Median 10.5y 6y NA ? Range 20d ~ 50y 6m ~ 42y NA ? * P < 0.05; SLE = systemic lupus erythematosus; M = median; IQR = interquartile range; d = days; m = months; y = years. Clinical manifestations and laboratory examinations of SLE patients The comparison of clinical manifestations between LR group and non-LR group is shown in Table 2 . The median SLEDAI score of the LR group was 18 (IQR = 7), which is significantly higher than that of non- LR group (9[5], P < 0.001 by U test) (Table 2 ). The frequency of pleuritis is significantly higher in LR group than in non-LR group (40% versus 20.4%, P = 0.044 by Chi-square test) (Table 2 ). Table 2 Clinical manifestations of SLE patients Item LR group n = 34 non-LR group n = 55 t/U/χ2 P value SLEDAI, M (IQR) 18 (7) 9 (5) 197.500 < 0.001* Fever, n (%) 25 (71.4) 37 (68.5) 0.085 0.771 Tmax during fever (℃), mean ± SD 38.887 ± 0.693 38.943 ± 0.741 -0.288 0.774 Erythra, n (%) 13 (37.1%) 26 (48.1%) 1.045 0.307 Butterfly erythema, n (%) 16 (45.7%) 21 (38.9%) 0.407 0.523 Arthritis, n (%) 22 (62.9%) 36 (66.7%) 0.136 0.713 Alopecia, n (%) 18 (51.4%) 20 (37.0%) 1.798 0.180 Canker sore, n (%) 13 (37.1%) 11 (20.4%) 3.033 0.082 Photoallergy, n (%) 5 (14.3%) 12 (22.2%) 0.866 0.352 Reynolds phenomenon, n (%) 6 (17.1%) 12 (22.2%) 0.340 0.560 Urinary occult blood, n (%) 15 (42.9%) 13 (24.1%) 3.475 0.062 Urinary albumin, n (%) 20 (57.1%) 26 (48.1%) 0.688 0.407 Pleuritis, n (%) 14 (40.0%) 11 (20.4%) 4.051 0.044* Pericarditis, n (%) 10 (28.6%) 10 (18.5%) 1.232 0.267 * P < 0.05; SLEDAI = systemic lupus erythematosus disease activity index; SD = standard deviation; M = median; IQR = interquartile range; Tmax = maximum body temperature. The comparison of laboratory examinations between LR group and non-LR group is shown in Table 3 . All examination results showed no significant difference except hemoglobin which was lower in LR group than in non-LR group (102.343 ± 23.157 versus 112.759 ± 19.678, P = 0.025 by t test) (Table 3 ). Table 3 Laboratory examinations of SLE patients Item LR group n = 34 non-LR group n = 54 t/U/χ 2 P value CRP (mg/L), M (IQR) 2.100 (6.880) 1.210 (6.830) 863.500 0.491 ESR (mm/h), M (IQR) 27.500 (33.750) 18.000 (31.000) 741.500 0.130 IgA (g/L), M (IQR) 2.340 (1.820) 2.425 (1.690) 924.000 0.860 IgG (g/L), M (IQR) 13.100 (7.120) 11.800 (7.880) 785.000 0.179 IgM (g/L), M (IQR) 0.720 (0.790) 0.899 (0.860) 839.000 0.498 C3 (g/L), mean ± SD 0.638 ± 0.341 0.699 ± 0.271 -0.929 0.355 C4 (g/L), M (IQR) 0.130 (0.130) 0.160 (0.150) 765.500 0.131 WBC (10 9 /L), M (IQR) 5.900 (5.400) 5.650 (3.860) 787.500 0.186 Hb (g/L), mean ± SD 102.343 ± 23.157 112.759 ± 19.678 -2.274 0.025* PLT (10 9 /L), mean ± SD 176.200 ± 80.658 185.704 ± 74.831 -0.568 0.572 Anti-dsDNA Ab (+), n (%) 16 (45.7%) 22 (40.7%) 0.215 0.643 ANA (+), n (%) 31 (88.6%) 52 (96.3%) 0.974 0.324 Anti-Sm Ab (+), n (%) 3 (8.6%) 12 (22.2%) 2.824 0.093 Anti-U1 RNP Ab (+), n (%) 11 (31.4%) 19 (35.2%) 0.134 0.714 Anti-SSA Ab (+), n (%) 14 (40.0%) 27 (50.0%) 0.855 0.355 Anti-SSB Ab (+), n (%) 2 (5.7%) 4 (7.4%) 0.999 * P < 0.05; CRP = C-reactive protein; ESR = erythrocyte sedimentation rate; IgA = immunoglobulin A; IgG = immunoglobulin G; IgM = immunoglobulin M; C3 = complement 3; C4 = complement 4; WBC = white blood cell count; Hb = hemoglobin; PLT = blood platelet count; dsDNA = double stranded DNA; U1 RNP = U1 ribonucleoprotein; Anti-SSA Ab = anti-Sjo gren syndrome A antibody; Anti-SSB Ab = anti-Sjo gren syndrome B antibody; SD = standard deviation; M = median; IQR = interquartile range. Fundus manifestations and retinal features of fundus group In LR group, fundus examinations revealed various abnormalities: retinal hemorrhage (16/34, 47.1%), soft exudates (cotton-wool spots) (9/34, 26.5%), retinal vasculitis (8/34, 23.5%), macular edema (2/34, 5.9%), retinal artery occlusion (2/34, 5.9%), retinal vein occlusion (3/34, 8.8%), papilledema (2/34, 5.9%), optic atrophy (2/34, 5.9%), retinal detachment (1/34, 2.9%), vitreous hemorrhage (1/34, 2.9%) and choroidal detachment (1/34, 2.9%). Levels of ARAs The level of ARAs in enrolled participants is shown in Table 4 and Fig. 1 . LR group had higher level of anti-α-enolase Ab compared with non-LR group (12.470 (3.380) versus 10.362 (5.130) ng/mL, P = 0.033 by Dunn test) (Table 4 ). Additionally, both LR group and non-LR group had a significantly higher level of anti-α-enolase Ab than control group (12.470 (3.380) versus 6.652 (3.690) ng/mL, P < 0.0001 by Dunn test; 10.362 (5.130) versus 6.652 (3.690) ng/mL, P < 0.0001 by Dunn test) (Table 4 ). Level of anti-recoverin Ab were significantly higher in LR group than in non-LR group (254.539 ± 80.135 versus 213.219 ± 90.886 µg/mL, P = 0.036 by Scheffe test) (Table 4 ) and control group (254.539 ± 80.135 versus 185.150 ± 45.959 µg/mL, P < 0.0001 by Scheffe test) (Table 4 ). While there is no significant difference between non-LR group and control group (213.219 ± 90.886 versus 185.150 ± 45.959 µg/mL, P = 0.109 by Scheffe test) (Table 4 ). Level of anti-arrestin Ab in three groups were 2449.660 (1795.120) ng/L in LR group, 2507.970 (1747.840) ng/L in non-LR group and 2766.200 (2014.000) ng/L in control group respectively and there was no statistical difference among these three groups (H = 5.488, P = 0.064 by Kruskal-Wallis test) (Table 4 ). Both LR group and non-LR group had a significantly higher level of anti-IRBP3 Ab than negative control group (195.098 (100.190) versus 142.263 (65.150) ng/L, P = 0.024 by Dunn test; 239.929 (219.040) versus 142.263 (65.150) ng/L, P < 0.0001 by Dunn test) (Table 4 ). While level of anti-IRBP3 Ab between LR group and non-LR group showed no significant difference (195.098(100.190) versus 239.929 (219.040) ng/L, P = 0.838 by Dunn test) (Table 4 ). Table 4 The level of ARAs of all participants ARAs LR group non-LR group control group H/F P value anti-α-enolase Ab/ng/mL, M (IQR) 12.470 (3.380) 10.362 (5.130) 6.652 (3.690) 53.713 < 0.001* anti-arrestin Ab /ng/L, M (IQR) 2449.660 (1795.120) 2616.260 (2723.910) 2617.551 (630.500) 2.979 0.226 anti-recoverin Ab/µg/mL, mean ± SD 254.539 ± 80.135 213.219 ± 90.886 185.150 ± 45.959 11.556 < 0.001* anti-IRBP3 Ab/ng/L, M (IQR) 195.098 (100.190) 239.929 (219.040) 142.263 (65.150) 21.202 < 0.001* * P < 0.05; IRBP3 = interphotoreceptor retinol binding protein 3; SD = standard deviation; M = median; IQR = interquartile range. In order to further evaluate the diagnostic power of anti-α-enolase Ab and anti-recoverin Ab in LR, receiver operating characteristic curve (ROC) was produced according to the level of these two antibodies, alone and in combination (shown in Table 5 and Fig. 2 ). When using anti-α-enolase Ab alone, the area under curve (AUC) was 0.6565 (P = 0.0153). When using a cutoff value of 8.67 ng/mL, the sensitivity and specificity of anti-α-enolase Ab alone for diagnosing LR was 36.0% and 100.0%, respectively. When using anti-recoverin Ab alone, the AUC was 0.6196 (P = 0.0700). When using a cutoff value of 261.00µg/mL, the sensitivity and specificity of anti-recoverin Ab alone for diagnosing LR was 80.0% and 44.1%, respectively. When using anti-α-enolase Ab combined with anti-recoverin Ab, the AUC was 0.7268 (P = 0.0006). Using a cutoff value of 0.3968, and the sensitivity and specificity of the combination of these two Ab for diagnosing LR was 62.2% and 79.4%, respectively. Table 5 Summary of ROC curve results Classification AUC P Value cutoff value sensitivity/% specificity/% anti-α-enolase Ab 0.6565 0.0153* 8.6700 36.0 100.0 anti-recoverin Ab 0.6196 0.0700 261.0000 80.0 44.1 combination of anti-α-enolase and anti-recoverin Ab 0.7268 0.0006*** 0.3968 62.2 79.4 * P < 0.05; *** P < 0.001; AUC = area under curve. Discussion In this study, the fundus manifestations of the LR group were diverse, including retinal hemorrhage, cotton-wool spots, retinal vasculitis, macular edema, retinal artery occlusion, retinal vein occlusion, papilledema, optic atrophy, retinal detachment, vitreous hemorrhage and choroidal detachment. The most common fundus abnormalities in our enrolled patients were retinal hemorrhage (47.1%), cotton-wool spots (26.5%) and retinal vasculitis (23.5%). This result was consistent with previous reports, indicating good representative features of LR group enrolled in this study. However, due to the lack of a recognized grading scale for LR and the diversity of manifestations among LR in different phase, we did not analyze the correlation between the severity of fundus abnormalities and hematological indicators in this study. We consider to score fundus manifestations more specifically and further analyze the relationship between the severity of fundus lesions and the severity of systemic lesions and serological markers in future studies. LR group had a higher SLEDAI score than non-LR group, suggesting that patients with LR had higher disease activity, which was consistent with previous studies. However, it should be noted that in recent years, SLEDAI have included LR into the scoring rules, assigning a score of 8 points. If we subtracted these 8 points and then compared the left SLEDAI score of LR and non-LR, the difference between two groups was not statistically significant (U = 831.500, P = 0.380), suggesting that there may not be a definite association between LR and other general systemic lesion in SLE, this finding was similar to what Bashiri et al. reported in 2021. However, our study found that LR group had higher frequency of pleurisy and lower level of hemoglobin, suggesting that there may be a link between LR and some specific systemic manifestations, which needs larger sample sizes investigation to confirm. Our previous study has found that the serum level of anti-recoverin Ab increased in SLE patients with LR, 33 however, due to the lack of data on specific manifestations of fundus lesions in previous studies, we could not know whether there was selective bias. In this study, we found that the level of anti-recoverin Ab was significantly higher in LR group than in non-LR group and control group, and no difference between the latter two groups was observed, which further confirmed our previous studies. Previous publications report anti-α-enolase Ab was observed positive in 27.14%(19/70) of autoimmune diseases patients and 45.8%(11/24) of SLE patients, 34 and the serum level of anti-α-enolase Ab in the disease group was significantly higher than the healthy group. 35 Huang et al. suggested that anti-α enolase Ab combined with urinary β2 microglobulin can predict the incidence of nephritis in SLE patients with a sensitivity of 92% and specificity of 93%. 11 In this study, the serum anti-α-enolase Ab level in LR group was elevated compared with non-LR group and the AUC was 0.6565 when predicting LR by this antibody alone. No correlation was found between LR and kidney involvement biomarker such as urinary occulted blood and urinary albumin. Considering the structural similarity between retina and glomerulus, the level of urinary β2 microglobulin can be investigated in future studies to observe whether there is a certain correlation between its level and LR. The difference in serum anti-arrestin Ab levels among the three groups was not statistically significant and there was no statistically significant difference in the level of anti-IRBP3 Ab between LR group and non-LR group in this study. One possible explanation may be because these two Ab were only expressed in the retinal photoreceptor and the damage of photoreceptor cells often occurs secondary to deep retinal ischemia and hypoxia and may not be affected in all patient especially in the early stage. Optical coherence tomography (OCT) could be a valuable tool for the assessment of photoreceptor damage, but unfortunately the OCT images of most of our participants were lacking. Our study has many limitations. Firstly, the sample size is small, especially in the LR group and it is difficult to avoid selection bias during the analysis of results. Secondly, some possible biomarkers which may be associated with LR were not included in our study, such as urinary β2 microglobulin, as we mentioned above. Thirdly, this study only analyzed ARAs in blood sample and their level in aquas humor might be different to its serum. Further studies are needed to provide more solid data on the level of ARAs in aqueous humor and exploring their association between them and LR. In conclusion, this study is the first to evaluate the association between serum anti-retinal antibodies levels of SLE patients and the incidence of lupus retinopathy. We found SLE patients with LR had higher frequency of pleurisy and lower level of hemoglobin compared with SLE patients without LR. Anti-α-enolase Ab and anti-recoverin Ab may be used as potential biomarkers of lupus retinopathy in SLE patients, and the combined diagnostic effect is better than these two antibodies alone. Methods Participants This study enrolled 170 subjects (including 89 SLE patients and 81 age-and sex-matched healthy controls) at Peking University People’s Hospital between September 2020 and July 2022. SLE patients were further divided into 2 groups (LR group and non-LR group) according to the presence of lupus retinopathy, which was diagnosed according to fundus manifestations. Inclusion & exclusion criteria The inclusion criteria were as follows: (1) age ≥ 18 years, (2) SLE patients fulfilled the revised 2009 European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) classification criteria for SLE, (3) subjects without any other eye disease or any systemic disease were enrolled as controls, (4) agree to sign informed consents. The exclusion criteria were as follows: (1) clinical manifestations or laboratory examinations suggest a history of past or present infection or malignant tumor, (2) breastfeeding or being pregnant (3) history of taking medications that may cause fundus lesions, such as steroids or hydroxychloroquine (HCQ), (4) presence of retinal diseases other than LR, such as diabetic retinopathy or macular degeneration, (5) presence of any undetermined retinal condition, (6) unable to undertake ophthalmologic examinations, (7) subjects with high bilirubin blood samples, chylous blood samples or hemolysis, (8) subjects with coagulation disorders, (9) subjects taken immunosuppressants or biological agents. Data extraction Basic information, venous blood samples and laboratory test result within one week from the blood sample collection date were recorded and SLE Disease Activity Index 2000 (SLEDAI-2K), a global index based on the symptoms and laboratory findings was calculated according to medical records from each SLE patient. All enrolled subjects underwent systemic examinations, laboratory test and ophthalmic examinations, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), fundoscopy and color fundus photography after mydriasis. All SLE patients with lupus retinopathy underwent further optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) examination. ELISA The serum obtained from all participants were subjected to ELISA (78687186-X, Beijing Weilaibo Biotechnology, China), according to the manufacturer’s instructions. Briefly, the calibration standards were measured at the same time as the samples. After the stop solution changed the color from blue to yellow, the intensity of the color was measured at 450 nm using a spectrophotometer. Standard curve was produced and the concentration of anti-α-enolase, anti-arrestin and anti-IRBP3 in the samples was determined respectively by comparing the OD of the samples to the standard curve. Statistical analysis Statistical analyses were carried out using SPSS 26.0 and GraphPad Prism 9.5.0. The variables were tested for normal distribution using the Kolmogorov-Smirnov test. Normally distributed variables were displayed as mean ± SD (standard deviation) and compared by independent t-test (between two groups). Non-normally distributed variables were displayed as M(IQR) (median (interquartile range)) and compared by Mann–Whitney U test (between two groups). Comparison of categorical variables, expressed as numbers, frequency and percentages, were done using Chi-square test. Correlations between continuous normally distributed and non-normally distributed variables were assessed by calculating Pearson correlation coefficients and Spearman’s rank correlation coefficients respectively. Receiver Operating Characteristic Curve (ROC) and Area Under Curve (AUC) were used to evaluate the diagnostic effect of ARAs in lupus retinopathy. The P value was two-tailed and considered as statistically significant for P < 0.05. Declarations Contributions Jinfeng Qu and Xuewu Zhang conceived and designed the experiments. Qingyi Zou, Linqi Zhang, Yu Cao, Bohao Wang and Muzi Li performed the experiments. Linqi Zhang analyzed the data. Qingyi Zou wrote the manuscript. All authors reviewed the manuscript. Qingyi Zou and Linqi Zhang contribute equally to this paper and are both considered the first author. Competing interests The author(s) declare no competing interests. Ethics declarations The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Peking University People’s Hospital. Informed consent was obtained from all subjects involved in the study. Funding This study was supported by Beijing Natural Science Foundation (Grant No. 7232192). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. Author Contribution Jinfeng Qu and Xuewu Zhang conceived and designed the experiments. Qingyi Zou, Linqi Zhang, Yu Cao, Bohao Wang and Muzi Li performed the experiments. Linqi Zhang analyzed the data. Qingyi Zou wrote the manuscript. All authors reviewed the manuscript. Qingyi Zou and Linqi Zhang contribute equally to this paper and are both considered the first author. Acknowledgement We gratefully acknowledge the financial support for this work from Beijing Natural Science Foundation (Grant No. 7232192). We also thank Dr. Li Zhu for her invaluable assistance with experimental setups and statistical analysis. Furthermore, we acknowledge the support from Beijing Key Laboratory of Ocular Disease and Optometry Science of Peking University People’s Hospital for providing the characterization facilities. Data Availability All data generated or analysed during this study are included in this published article (and its Supplementary Information files). References Fortuna, G. & Brennan, M. T. Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. Dent. Clin. North. Am. 57 , 631–655 (2013). Dammacco, R. Systemic lupus erythematosus and ocular involvement: an overview. Clin. Exp. Med. 18 , 135–149 (2018). de Andrade, F. A. et al. Neuro-ophthalmologic manifestations in systemic lupus erythematosus. 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J. & Shenoy, S. K. Transduction of receptor signals by beta-arrestins. Science 308 , 512–517 (2005). Nair, K. S. et al. Light-dependent redistribution of arrestin in vertebrate rods is an energy-independent process governed by protein-protein interactions. Neuron 46 , 555–567 (2005). Stanford, M. R. & Robbins, J. Experimental posterior uveitis. II. Electroretinographic studies. Br. J. Ophthalmol. 72 , 88–96 (1988). Gonzalez-Fernandez, F. & Ghosh, D. Focus on Molecules: interphotoreceptor retinoid-binding protein (IRBP). Exp. Eye Res. 86 , 169–170 (2008). Gonzalez-Fernandez, F. Interphotoreceptor retinoid-binding protein–an old gene for new eyes. Vis. Res. 43 , 3021–3036 (2003). Yang, J. M. et al. Multimodal evaluation of an interphotoreceptor retinoid-binding protein-induced mouse model of experimental autoimmune uveitis. Exp. Mol. Med. 54 , 252–262 (2022). Bowers, C. E., Calder, V. L., Greenwood, J. & Eskandarpour, M. Experimental Autoimmune Uveitis: An Intraocular Inflammatory Mouse Model. J Vis. Exp (2022). Li, M. et al. Anti-recoverin antibodies indicate fundus abnormalities in systemic lupus erythematosus. Lupus 29 , 1346–1352 (2020). He, Z. et al. [Detection and analysis of serum level of anti-Candida enolase IgG antibody in patients with autoimmune diseases]. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi . 33 , 1113–1117 (2017). Huang, Y. et al. Evaluation of systemic lupus erythematosus disease activity using anti-α-enolase antibody and RDW. Clin. Exp. Med. 21 , 73–78 (2021). Additional Declarations No competing interests reported. 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06:30:32","extension":"xml","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":100916,"visible":true,"origin":"","legend":"","description":"","filename":"d4c4f825ee7b468aa4688283359dc6d01structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/cac3305a1e15137c3fac9cf7.xml"},{"id":96788128,"identity":"a5310d3e-7a9b-4a7d-81bd-79c42ac39ec7","added_by":"auto","created_at":"2025-11-26 06:30:32","extension":"html","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":109919,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/45cc801f5bcc202db20fe1c5.html"},{"id":96788122,"identity":"72d9f7b5-87cd-4515-a2c7-1867c6df723b","added_by":"auto","created_at":"2025-11-26 06:30:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":241992,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe level of ARAs in LR group, non-LR group and control group.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/4fd969f0ee33bd5c0fae0065.png"},{"id":96916569,"identity":"b6a1b5b4-925a-4e3f-921b-25c5cfe22554","added_by":"auto","created_at":"2025-11-27 14:08:44","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":142485,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eReceiver operating characteristic (ROC) curve for evaluating LR by anti-α-enolase Ab and anti-recoverin Ab.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/236c0583068ddf1fcf433163.png"},{"id":104739582,"identity":"403a0d0d-9a20-47e3-a3ed-b269bc94df46","added_by":"auto","created_at":"2026-03-16 16:09:46","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1223493,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/e72a7d2f-2396-49f3-8bad-8ead6f5f71fa.pdf"},{"id":96788119,"identity":"dfe49e43-a4a3-413c-be97-23164cd8981a","added_by":"auto","created_at":"2025-11-26 06:30:32","extension":"xlsx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":24585,"visible":true,"origin":"","legend":"","description":"","filename":"antibodies.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-7950771/v1/26fcfa3b3ba9f9b6f0187fa9.xlsx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Correlation between anti-retinal antibodies and lupus retinopathy in systemic lupus erythematosus","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSystemic lupus erythematosus (SLE) is a chronic connective tissue disease with a wide range of clinical manifestations, characterized by production of autoantibodies directed against nuclear and cytoplasmic antigens which can affect various organs and systems.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eLupus retinopathy (LR) is one of the most frequent and serious complications of SLE, which may cause irreversible visual impairment.\u003csup\u003e\u003cspan additionalcitationids=\"CR3 CR4 CR5 CR6 CR7 CR8\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e Early diagnosis of LR can be helpful to predict and prevent severe visual impairment. Therefore, development of optimal diagnostic biomarker for LR in SLE patients is highly necessary.\u003c/p\u003e\u003cp\u003eRecoverin is a calcium-binding protein (molecular weight 23kDa), which inhibits the activity of rhodopsin kinase and regulates the phosphorylation of rhodopsin. It exists in the inner segment and nucleus of photoreceptors and the outer plexiform layer of retina.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e Anti-recoverin Ab can activated Caspase-9 and Caspase-3 dependent apoptotic pathways by inducing calcium ion influx and cause apoptosis of retinal photoreceptors.\u003csup\u003e\u003cspan additionalcitationids=\"CR12 CR13\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003ePrevious studies have reported that anti-retinal antibodies (ARAs) are associated with autoimmune retinopathy (AIR),\u003csup\u003e15\u0026ndash;18\u003c/sup\u003e diabetic retinopathy,\u003csup\u003e19\u003c/sup\u003e central serous chorioretinopathy,\u003csup\u003e20\u003c/sup\u003e macular telangiectasia type 2\u003csup\u003e21\u003c/sup\u003e and some genetic retinopathies such as retinopigmentosa, while the mechanisms of the induction of ARAs and their correlation with LR remained unknown.\u003c/p\u003e\u003cp\u003eAlpha-enolase (ENO1) is a subtype of enolase, which has a molecular weight of 46kDa, and catalyzed the production of ATP during glycolysis. It is widely expressed in vascular endothelial cells, cone outer segments, M\u0026uuml;ller cells and the ganglion cell layer of the retina.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e ENO1 is closely related to inflammation, autoimmune response, tumor and mitochondria function. Anti-α-enolase plays a pathogenic role by generating immune complexes, increasing intracellular calcium ion concentration and initiating apoptosis.\u003csup\u003e\u003cspan additionalcitationids=\"CR24\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eArrestin-1 (also named S antigen) is a soluble cytoplasmic protein (molecular weight 48kDa) which is specifically expressed in the photoreceptors. It plays an important role in signal regulation viva binding to G protein-coupled receptors, membrane receptors and a variety of intracellular soluble proteins.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Anti-arrestin Ab is involved in the conversion of light and dark adaptation by simple diffusion.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eIRBP3 is a sugar lipoprotein about 143kDa, which is the main soluble protein in the photoreceptor matrix. It is secreted by photoreceptor cells, and its main physiological role is to regulate the function of cones, rods, M\u0026uuml;ller cells and retinal pigment epithelium,\u003csup\u003e29\u003c/sup\u003e and provide retinol and retinoic acid to the retina. In addition, the protein protects the unstable molecules from oxidation and isomerization.\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Adequate amounts of IRBP3 are therefore essential for the structural and functional integrity of the retina, especially photoreceptor cells. Currently, IRBP is considered to be involved in autoimmune uveitis and is one of the antigens of spontaneous uveitis in humans and animals.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e,\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\u003cp\u003eThe aim of this study was to evaluate the association between these four ARAs levels and the incidence of LR in SLE patients.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eCharacteristics of participants\u003c/h2\u003e\u003cp\u003eThere are 34 SLE patients in LR group, 55 SLE patients in non-LR group and 81 patients as controls enrolled in this study. Their clinical characteristics are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age of LR group, non-LR group and control group was 44.5(29), 34(23) and 58(47) respectively. The median age in control group was significant older than in non-LR group (P\u0026thinsp;=\u0026thinsp;0.026). The proportion of female subjects were significant lower in control group (56/81, 69.1%) than in LR group (27/34, 79.4%) and non-LR group (49/55, 89.1%) (P\u0026thinsp;=\u0026thinsp;0.022, by Chi-square test) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The median SLE duration of LR group and non- LR group was 10.5 years and 6 years, ranging from 20 days to 50 years and 6 months to 42 years 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\u003e\u003cb\u003eCharacteristics of participants\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eItem\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLR group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enon-LR group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003econtrol group\u003c/p\u003e\u003cp\u003e(n\u0026thinsp;=\u0026thinsp;81)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eAge/year, M(IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44.5 (29)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e34 (23)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e58 (47)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.031*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAge range\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18ཞ73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e17ཞ81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e17ཞ87\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGender, n (%)\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (20.60)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6 (10.90)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e25 (30.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0.022*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFemale\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e27 (79.40)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e49 (89.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e56 (69.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSLE duration/year\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\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.5y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e?\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRange\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20d\u0026thinsp;~\u0026thinsp;50y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6m\u0026thinsp;~\u0026thinsp;42y\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e?\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05; SLE\u0026thinsp;=\u0026thinsp;systemic lupus erythematosus; M\u0026thinsp;=\u0026thinsp;median; IQR\u0026thinsp;=\u0026thinsp;interquartile range; d\u0026thinsp;=\u0026thinsp;days; m\u0026thinsp;=\u0026thinsp;months; y\u0026thinsp;=\u0026thinsp;years.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eClinical manifestations and laboratory examinations of SLE patients\u003c/h3\u003e\n\u003cp\u003eThe comparison of clinical manifestations between LR group and non-LR group is shown in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The median SLEDAI score of the LR group was 18 (IQR\u0026thinsp;=\u0026thinsp;7), which is significantly higher than that of non- LR group (9[5], P\u0026thinsp;\u0026lt;\u0026thinsp;0.001 by U test) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The frequency of pleuritis is significantly higher in LR group than in non-LR group (40% versus 20.4%, P\u0026thinsp;=\u0026thinsp;0.044 by Chi-square test) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003e\u003cb\u003eClinical manifestations of SLE patients\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eItem\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLR group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enon-LR group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;55\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003et/U/χ2\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eSLEDAI, M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18 (7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9 (5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e197.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\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\u003e25 (71.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37 (68.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.085\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.771\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTmax during fever (℃), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e38.887\u0026thinsp;\u0026plusmn;\u0026thinsp;0.693\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.943\u0026thinsp;\u0026plusmn;\u0026thinsp;0.741\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.288\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.774\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eErythra, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (37.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (48.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.045\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.307\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eButterfly erythema, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16 (45.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e21 (38.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.407\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.523\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\u003e22 (62.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36 (66.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.136\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.713\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\u003e18 (51.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20 (37.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.798\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.180\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCanker sore, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (37.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (20.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.033\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.082\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePhotoallergy, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e5 (14.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.866\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.352\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eReynolds phenomenon, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e6 (17.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.340\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.560\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary occult blood, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e15 (42.9%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13 (24.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e3.475\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.062\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUrinary albumin, n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20 (57.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26 (48.1%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.688\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.407\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\u003e14 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e11 (20.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e4.051\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.044*\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\u003e10 (28.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10 (18.5%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e1.232\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.267\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05; SLEDAI\u0026thinsp;=\u0026thinsp;systemic lupus erythematosus disease activity index; SD\u0026thinsp;=\u0026thinsp;standard deviation; M\u0026thinsp;=\u0026thinsp;median; IQR\u0026thinsp;=\u0026thinsp;interquartile range; Tmax\u0026thinsp;=\u0026thinsp;maximum body temperature.\u003c/p\u003e\u003cp\u003eThe comparison of laboratory examinations between LR group and non-LR group is shown in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. All examination results showed no significant difference except hemoglobin which was lower in LR group than in non-LR group (102.343\u0026thinsp;\u0026plusmn;\u0026thinsp;23.157 versus 112.759\u0026thinsp;\u0026plusmn;\u0026thinsp;19.678, P\u0026thinsp;=\u0026thinsp;0.025 by t test) (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\u003e\u003cb\u003eLaboratory examinations of SLE patients\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"5\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eItem\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLR group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enon-LR group\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;54\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cem\u003et/U/χ\u003c/em\u003e\u003csup\u003e\u003cem\u003e2\u003c/em\u003e\u003c/sup\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\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\u003eCRP (mg/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.100 (6.880)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e1.210 (6.830)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e863.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.491\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESR (mm/h), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27.500 (33.750)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e18.000 (31.000)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e741.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.130\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgA (g/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.340 (1.820)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e2.425 (1.690)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e924.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.860\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgG (g/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e13.100 (7.120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e11.800 (7.880)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e785.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.179\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIgM (g/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.720 (0.790)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.899 (0.860)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e839.000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.498\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC3 (g/L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.638\u0026thinsp;\u0026plusmn;\u0026thinsp;0.341\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.699\u0026thinsp;\u0026plusmn;\u0026thinsp;0.271\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.929\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.355\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eC4 (g/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.130 (0.130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.160 (0.150)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e765.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.131\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWBC (10\u003csup\u003e9\u003c/sup\u003e/L), M (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.900 (5.400)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e5.650 (3.860)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e787.500\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.186\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHb (g/L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e102.343\u0026thinsp;\u0026plusmn;\u0026thinsp;23.157\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e112.759\u0026thinsp;\u0026plusmn;\u0026thinsp;19.678\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-2.274\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.025*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePLT (10\u003csup\u003e9\u003c/sup\u003e/L), mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e176.200\u0026thinsp;\u0026plusmn;\u0026thinsp;80.658\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e185.704\u0026thinsp;\u0026plusmn;\u0026thinsp;74.831\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e-0.568\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.572\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-dsDNA Ab (+), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16 (45.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e22 (40.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.215\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.643\u003c/p\u003e\u003c/td\u003e\u003c/tr\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\u003e31 (88.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e52 (96.3%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.974\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.324\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-Sm Ab (+), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3 (8.6%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e12 (22.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e2.824\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.093\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-U1 RNP Ab (+), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11 (31.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e19 (35.2%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.134\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.714\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-SSA Ab (+), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e14 (40.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e27 (50.0%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.855\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e0.355\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAnti-SSB Ab (+), n (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2 (5.7%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e4 (7.4%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e\u0026gt;\u0026thinsp;0.999\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"5\"\u003e*\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05; CRP\u0026thinsp;=\u0026thinsp;C-reactive protein; ESR\u0026thinsp;=\u0026thinsp;erythrocyte sedimentation rate; IgA\u0026thinsp;=\u0026thinsp;immunoglobulin A; IgG\u0026thinsp;=\u0026thinsp;immunoglobulin G; IgM\u0026thinsp;=\u0026thinsp;immunoglobulin M; C3\u0026thinsp;=\u0026thinsp;complement 3; C4\u0026thinsp;=\u0026thinsp;complement 4; WBC\u0026thinsp;=\u0026thinsp;white blood cell count; Hb\u0026thinsp;=\u0026thinsp;hemoglobin; PLT\u0026thinsp;=\u0026thinsp;blood platelet count; dsDNA\u0026thinsp;=\u0026thinsp;double stranded\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eDNA; U1 RNP\u0026thinsp;=\u0026thinsp;U1 ribonucleoprotein; Anti-SSA Ab\u0026thinsp;=\u0026thinsp;anti-Sjo gren syndrome A antibody; Anti-SSB Ab\u0026thinsp;=\u0026thinsp;anti-Sjo gren syndrome B antibody; SD\u0026thinsp;=\u0026thinsp;standard deviation; M\u0026thinsp;=\u0026thinsp;median; IQR\u0026thinsp;=\u0026thinsp;interquartile range.\u003c/p\u003e\n\u003ch3\u003eFundus manifestations and retinal features of fundus group\u003c/h3\u003e\n\u003cp\u003eIn LR group, fundus examinations revealed various abnormalities: retinal hemorrhage (16/34, 47.1%), soft exudates (cotton-wool spots) (9/34, 26.5%), retinal vasculitis (8/34, 23.5%), macular edema (2/34, 5.9%), retinal artery occlusion (2/34, 5.9%), retinal vein occlusion (3/34, 8.8%), papilledema (2/34, 5.9%), optic atrophy (2/34, 5.9%), retinal detachment (1/34, 2.9%), vitreous hemorrhage (1/34, 2.9%) and choroidal detachment (1/34, 2.9%).\u003c/p\u003e\n\u003ch3\u003eLevels of ARAs\u003c/h3\u003e\n\u003cp\u003eThe level of ARAs in enrolled participants is shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003eLR group had higher level of anti-α-enolase Ab compared with non-LR group (12.470 (3.380) versus 10.362 (5.130) ng/mL, P\u0026thinsp;=\u0026thinsp;0.033 by Dunn test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Additionally, both LR group and non-LR group had a significantly higher level of anti-α-enolase Ab than control group (12.470 (3.380) versus 6.652 (3.690) ng/mL, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001 by Dunn test; 10.362 (5.130) versus 6.652 (3.690) ng/mL, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001 by Dunn test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLevel of anti-recoverin Ab were significantly higher in LR group than in non-LR group (254.539\u0026thinsp;\u0026plusmn;\u0026thinsp;80.135 versus 213.219\u0026thinsp;\u0026plusmn;\u0026thinsp;90.886 \u0026micro;g/mL, P\u0026thinsp;=\u0026thinsp;0.036 by Scheffe test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) and control group (254.539\u0026thinsp;\u0026plusmn;\u0026thinsp;80.135 versus 185.150\u0026thinsp;\u0026plusmn;\u0026thinsp;45.959 \u0026micro;g/mL, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001 by Scheffe test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). While there is no significant difference between non-LR group and control group (213.219\u0026thinsp;\u0026plusmn;\u0026thinsp;90.886 versus 185.150\u0026thinsp;\u0026plusmn;\u0026thinsp;45.959 \u0026micro;g/mL, P\u0026thinsp;=\u0026thinsp;0.109 by Scheffe test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eLevel of anti-arrestin Ab in three groups were 2449.660 (1795.120) ng/L in LR group, 2507.970 (1747.840) ng/L in non-LR group and 2766.200 (2014.000) ng/L in control group respectively and there was no statistical difference among these three groups (H\u0026thinsp;=\u0026thinsp;5.488, P\u0026thinsp;=\u0026thinsp;0.064 by Kruskal-Wallis test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eBoth LR group and non-LR group had a significantly higher level of anti-IRBP3 Ab than negative control group (195.098 (100.190) versus 142.263 (65.150) ng/L, P\u0026thinsp;=\u0026thinsp;0.024 by Dunn test; 239.929 (219.040) versus 142.263 (65.150) ng/L, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001 by Dunn test) (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). While level of anti-IRBP3 Ab between LR group and non-LR group showed no significant difference (195.098(100.190) versus 239.929 (219.040) ng/L, P\u0026thinsp;=\u0026thinsp;0.838 by Dunn test) (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\u003e\u003cb\u003eThe level of ARAs of all participants\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eARAs\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eLR group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003enon-LR group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003econtrol group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003e\u003cem\u003eH/F\u003c/em\u003e\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\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\u003eanti-α-enolase Ab/ng/mL,\u003c/p\u003e\u003cp\u003eM (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12.470\u003c/p\u003e\u003cp\u003e(3.380)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.362\u003c/p\u003e\u003cp\u003e(5.130)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e6.652\u003c/p\u003e\u003cp\u003e(3.690)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e53.713\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eanti-arrestin Ab /ng/L,\u003c/p\u003e\u003cp\u003eM (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2449.660 (1795.120)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2616.260 (2723.910)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2617.551 (630.500)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e2.979\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e0.226\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eanti-recoverin Ab/\u0026micro;g/mL, mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e254.539\u0026thinsp;\u0026plusmn;\u0026thinsp;80.135\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e213.219\u0026thinsp;\u0026plusmn;\u0026thinsp;90.886\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e185.150\u0026thinsp;\u0026plusmn;\u0026thinsp;45.959\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e11.556\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eanti-IRBP3 Ab/ng/L,\u003c/p\u003e\u003cp\u003eM (IQR)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e195.098 (100.190)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e239.929 (219.040)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e142.263 (65.150)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e21.202\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001*\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*\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05; IRBP3\u0026thinsp;=\u0026thinsp;interphotoreceptor retinol binding protein 3; SD\u0026thinsp;=\u0026thinsp;standard deviation; M\u0026thinsp;=\u0026thinsp;median; IQR\u0026thinsp;=\u0026thinsp;interquartile range.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eIn order to further evaluate the diagnostic power of anti-α-enolase Ab and anti-recoverin Ab in LR, receiver operating characteristic curve (ROC) was produced according to the level of these two antibodies, alone and in combination (shown in Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). When using anti-α-enolase Ab alone, the area under curve (AUC) was 0.6565 (P\u0026thinsp;=\u0026thinsp;0.0153). When using a cutoff value of 8.67 ng/mL, the sensitivity and specificity of anti-α-enolase Ab alone for diagnosing LR was 36.0% and 100.0%, respectively. When using anti-recoverin Ab alone, the AUC was 0.6196 (P\u0026thinsp;=\u0026thinsp;0.0700). When using a cutoff value of 261.00\u0026micro;g/mL, the sensitivity and specificity of anti-recoverin Ab alone for diagnosing LR was 80.0% and 44.1%, respectively. When using anti-α-enolase Ab combined with anti-recoverin Ab, the AUC was 0.7268 (P\u0026thinsp;=\u0026thinsp;0.0006). Using a cutoff value of 0.3968, and the sensitivity and specificity of the combination of these two Ab for diagnosing LR was 62.2% and 79.4%, respectively.\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\u003e\u003cb\u003eSummary of ROC curve results\u003c/b\u003e\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eClassification\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAUC\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u003cem\u003eP\u003c/em\u003e Value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003ecutoff value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003esensitivity/%\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003especificity/%\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eanti-α-enolase Ab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.6565\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0153*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e8.6700\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e36.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e100.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eanti-recoverin Ab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.6196\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0700\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e261.0000\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e80.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e44.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ecombination of anti-α-enolase and anti-recoverin Ab\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.7268\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e\u003cp\u003e0.0006***\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.3968\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e\u003cp\u003e62.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e\u003cp\u003e79.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e*\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.05; ***\u003cem\u003eP\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001; AUC\u0026thinsp;=\u0026thinsp;area under curve.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, the fundus manifestations of the LR group were diverse, including retinal hemorrhage, cotton-wool spots, retinal vasculitis, macular edema, retinal artery occlusion, retinal vein occlusion, papilledema, optic atrophy, retinal detachment, vitreous hemorrhage and choroidal detachment. The most common fundus abnormalities in our enrolled patients were retinal hemorrhage (47.1%), cotton-wool spots (26.5%) and retinal vasculitis (23.5%). This result was consistent with previous reports, indicating good representative features of LR group enrolled in this study. However, due to the lack of a recognized grading scale for LR and the diversity of manifestations among LR in different phase, we did not analyze the correlation between the severity of fundus abnormalities and hematological indicators in this study. We consider to score fundus manifestations more specifically and further analyze the relationship between the severity of fundus lesions and the severity of systemic lesions and serological markers in future studies.\u003c/p\u003e\u003cp\u003eLR group had a higher SLEDAI score than non-LR group, suggesting that patients with LR had higher disease activity, which was consistent with previous studies. However, it should be noted that in recent years, SLEDAI have included LR into the scoring rules, assigning a score of 8 points. If we subtracted these 8 points and then compared the left SLEDAI score of LR and non-LR, the difference between two groups was not statistically significant (U\u0026thinsp;=\u0026thinsp;831.500, P\u0026thinsp;=\u0026thinsp;0.380), suggesting that there may not be a definite association between LR and other general systemic lesion in SLE, this finding was similar to what Bashiri et al. reported in 2021. However, our study found that LR group had higher frequency of pleurisy and lower level of hemoglobin, suggesting that there may be a link between LR and some specific systemic manifestations, which needs larger sample sizes investigation to confirm.\u003c/p\u003e\u003cp\u003eOur previous study has found that the serum level of anti-recoverin Ab increased in SLE patients with LR,\u003csup\u003e33\u003c/sup\u003e however, due to the lack of data on specific manifestations of fundus lesions in previous studies, we could not know whether there was selective bias. In this study, we found that the level of anti-recoverin Ab was significantly higher in LR group than in non-LR group and control group, and no difference between the latter two groups was observed, which further confirmed our previous studies.\u003c/p\u003e\u003cp\u003ePrevious publications report anti-α-enolase Ab was observed positive in 27.14%(19/70) of autoimmune diseases patients and 45.8%(11/24) of SLE patients,\u003csup\u003e34\u003c/sup\u003e and the serum level of anti-α-enolase Ab in the disease group was significantly higher than the healthy group.\u003csup\u003e\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e\u003c/sup\u003e Huang et al. suggested that anti-α enolase Ab combined with urinary β2 microglobulin can predict the incidence of nephritis in SLE patients with a sensitivity of 92% and specificity of 93%.\u003csup\u003e11\u003c/sup\u003e In this study, the serum anti-α-enolase Ab level in LR group was elevated compared with non-LR group and the AUC was 0.6565 when predicting LR by this antibody alone. No correlation was found between LR and kidney involvement biomarker such as urinary occulted blood and urinary albumin. Considering the structural similarity between retina and glomerulus, the level of urinary β2 microglobulin can be investigated in future studies to observe whether there is a certain correlation between its level and LR.\u003c/p\u003e\u003cp\u003eThe difference in serum anti-arrestin Ab levels among the three groups was not statistically significant and there was no statistically significant difference in the level of anti-IRBP3 Ab between LR group and non-LR group in this study. One possible explanation may be because these two Ab were only expressed in the retinal photoreceptor and the damage of photoreceptor cells often occurs secondary to deep retinal ischemia and hypoxia and may not be affected in all patient especially in the early stage. Optical coherence tomography (OCT) could be a valuable tool for the assessment of photoreceptor damage, but unfortunately the OCT images of most of our participants were lacking.\u003c/p\u003e\u003cp\u003eOur study has many limitations. Firstly, the sample size is small, especially in the LR group and it is difficult to avoid selection bias during the analysis of results. Secondly, some possible biomarkers which may be associated with LR were not included in our study, such as urinary β2 microglobulin, as we mentioned above. Thirdly, this study only analyzed ARAs in blood sample and their level in aquas humor might be different to its serum. Further studies are needed to provide more solid data on the level of ARAs in aqueous humor and exploring their association between them and LR.\u003c/p\u003e\u003cp\u003eIn conclusion, this study is the first to evaluate the association between serum anti-retinal antibodies levels of SLE patients and the incidence of lupus retinopathy. We found SLE patients with LR had higher frequency of pleurisy and lower level of hemoglobin compared with SLE patients without LR. Anti-α-enolase Ab and anti-recoverin Ab may be used as potential biomarkers of lupus retinopathy in SLE patients, and the combined diagnostic effect is better than these two antibodies alone.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003cdiv id=\"Sec9\" class=\"Section3\"\u003e\u003ch2\u003eParticipants\u003c/h2\u003e\u003cp\u003eThis study enrolled 170 subjects (including 89 SLE patients and 81 age-and sex-matched healthy controls) at Peking University People\u0026rsquo;s Hospital between September 2020 and July 2022. SLE patients were further divided into 2 groups (LR group and non-LR group) according to the presence of lupus retinopathy, which was diagnosed according to fundus manifestations.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\n\u003ch3\u003eInclusion \u0026 exclusion criteria\u003c/h3\u003e\n\u003cp\u003eThe inclusion criteria were as follows: (1) age\u0026thinsp;\u0026ge;\u0026thinsp;18 years, (2) SLE patients fulfilled the revised 2009 European League Against Rheumatism (EULAR) or American College of Rheumatology (ACR) classification criteria for SLE, (3) subjects without any other eye disease or any systemic disease were enrolled as controls, (4) agree to sign informed consents.\u003c/p\u003e\u003cp\u003eThe exclusion criteria were as follows: (1) clinical manifestations or laboratory examinations suggest a history of past or present infection or malignant tumor, (2) breastfeeding or being pregnant (3) history of taking medications that may cause fundus lesions, such as steroids or hydroxychloroquine (HCQ), (4) presence of retinal diseases other than LR, such as diabetic retinopathy or macular degeneration, (5) presence of any undetermined retinal condition, (6) unable to undertake ophthalmologic examinations, (7) subjects with high bilirubin blood samples, chylous blood samples or hemolysis, (8) subjects with coagulation disorders, (9) subjects taken immunosuppressants or biological agents.\u003c/p\u003e\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eData extraction\u003c/h2\u003e\u003cp\u003eBasic information, venous blood samples and laboratory test result within one week from the blood sample collection date were recorded and SLE Disease Activity Index 2000 (SLEDAI-2K), a global index based on the symptoms and laboratory findings was calculated according to medical records from each SLE patient. All enrolled subjects underwent systemic examinations, laboratory test and ophthalmic examinations, including best-corrected visual acuity (BCVA), intraocular pressure (IOP), fundoscopy and color fundus photography after mydriasis. All SLE patients with lupus retinopathy underwent further optical coherence tomography (OCT) and fundus fluorescein angiography (FFA) examination.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eELISA\u003c/h2\u003e\u003cp\u003e The serum obtained from all participants were subjected to ELISA (78687186-X, Beijing Weilaibo Biotechnology, China), according to the manufacturer\u0026rsquo;s instructions. Briefly, the calibration standards were measured at the same time as the samples. After the stop solution changed the color from blue to yellow, the intensity of the color was measured at 450 nm using a spectrophotometer. Standard curve was produced and the concentration of anti-α-enolase, anti-arrestin and anti-IRBP3 in the samples was determined respectively by comparing the OD of the samples to the standard curve.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eStatistical analyses were carried out using SPSS 26.0 and GraphPad Prism 9.5.0. The variables were tested for normal distribution using the Kolmogorov-Smirnov test. Normally distributed variables were displayed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD (standard deviation) and compared by independent t-test (between two groups). Non-normally distributed variables were displayed as M(IQR) (median (interquartile range)) and compared by Mann\u0026ndash;Whitney U test (between two groups). Comparison of categorical variables, expressed as numbers, frequency and percentages, were done using Chi-square test. Correlations between continuous normally distributed and non-normally distributed variables were assessed by calculating Pearson correlation coefficients and Spearman\u0026rsquo;s rank correlation coefficients respectively. Receiver Operating Characteristic Curve (ROC) and Area Under Curve (AUC) were used to evaluate the diagnostic effect of ARAs in lupus retinopathy. The P value was two-tailed and considered as statistically significant for P\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e\u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eContributions\u003c/h2\u003e\u003cp\u003eJinfeng Qu and Xuewu Zhang conceived and designed the experiments. Qingyi Zou, Linqi Zhang, Yu Cao, Bohao Wang and Muzi Li performed the experiments. Linqi Zhang analyzed the data. Qingyi Zou wrote the manuscript. All authors reviewed the manuscript. Qingyi Zou and Linqi Zhang contribute equally to this paper and are both considered the first author.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eCompeting interests\u003c/h2\u003e\u003cp\u003eThe author(s) declare no competing interests.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003ch2\u003eEthics declarations\u003c/h2\u003e\u003cp\u003e The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Institutional Review Board (or Ethics Committee) of Peking University People\u0026rsquo;s Hospital. Informed consent was obtained from all subjects involved in the study.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was supported by Beijing Natural Science Foundation (Grant No. 7232192). The funders had no role in the study design, data collection and analysis, decision to publish or preparation of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJinfeng Qu and Xuewu Zhang conceived and designed the experiments. Qingyi Zou, Linqi Zhang, Yu Cao, Bohao Wang and Muzi Li performed the experiments. Linqi Zhang analyzed the data. Qingyi Zou wrote the manuscript. All authors reviewed the manuscript. Qingyi Zou and Linqi Zhang contribute equally to this paper and are both considered the first author.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe gratefully acknowledge the financial support for this work from Beijing Natural Science Foundation (Grant No. 7232192). We also thank Dr. Li Zhu for her invaluable assistance with experimental setups and statistical analysis. Furthermore, we acknowledge the support from Beijing Key Laboratory of Ocular Disease and Optometry Science of Peking University People\u0026rsquo;s Hospital for providing the characterization facilities.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eAll data generated or analysed during this study are included in this published article (and its Supplementary Information files).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eFortuna, G. \u0026amp; Brennan, M. T. Systemic lupus erythematosus: epidemiology, pathophysiology, manifestations, and management. \u003cem\u003eDent. Clin. North. Am.\u003c/em\u003e \u003cb\u003e57\u003c/b\u003e, 631\u0026ndash;655 (2013).\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eDammacco, R. Systemic lupus erythematosus and ocular involvement: an overview. \u003cem\u003eClin. Exp. 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Med.\u003c/em\u003e \u003cb\u003e21\u003c/b\u003e, 73\u0026ndash;78 (2021).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Systemic lupus erythematosus, lupus retinopathy, anti-α-enolase antibody, anti-arrestin antibody, anti-recoverin antibody, anti-IRBP3 antibody","lastPublishedDoi":"10.21203/rs.3.rs-7950771/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7950771/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eLupus retinopathy (LR) is one of the most frequent and serious complications of Systemic lupus erythematosus (SLE), because it may cause irreversible visual impairment. The aim of this study was to evaluate the association between serum anti-retinal antibodies levels of SLE patients and the incidence of LR. Levels of serum anti-α-enolase antibody (Ab), anti-arrestin Ab, anti-recoverin Ab and anti-IRBP3 Ab were detected in 89 SLE patients (further divided into LR group and non-LR group) and 81 healthy controls by enzyme-linked immunosorbent assay (ELISA). The correlation between these four anti-retinal Ab, SLE activity and the incidence of LR was evaluated by correlation analysis. LR group had a higher SLE disease activity index (SLEDAI, 18 (7) versus 9 (5), P\u0026thinsp;\u0026lt;\u0026thinsp;0.001), higher frequency of pleurisy (40% versus 20.4%, P\u0026thinsp;=\u0026thinsp;0.044) and lower level of hemoglobin (102.343\u0026thinsp;\u0026plusmn;\u0026thinsp;23.157 versus 112.759\u0026thinsp;\u0026plusmn;\u0026thinsp;19.678, P\u0026thinsp;=\u0026thinsp;0.025) comparing to non-LR group. LR group had higher levels of anti-α-enolase than non-LR group (P\u0026thinsp;=\u0026thinsp;0.033) and control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The levels of anti-recoverin in LR group was higher than non-LR group (P\u0026thinsp;=\u0026thinsp;0.036) and control group (P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001), while the difference was not significant between non-LR group and control group (P\u0026thinsp;=\u0026thinsp;0.109). Combination of anti-α-enolase Ab and anti-recoverin Ab for evaluating the incidence of LR in SLE patients had better effectiveness (area under the receiver operating characteristic curve (AUC): 72.68%) compared with only anti-α-enolase Ab (AUC: 65.65%) or anti-recoverin (AUC: 61.96%). Our results suggested that Anti-α-enolase and anti-recoverin may be used as potential biomarkers of lupus retinopathy in SLE patients.\u003c/p\u003e","manuscriptTitle":"Correlation between anti-retinal antibodies and lupus retinopathy in systemic lupus erythematosus","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-11-26 06:30:27","doi":"10.21203/rs.3.rs-7950771/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-29T19:59:31+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-23T23:59:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"206464531506574299714496317352082719077","date":"2025-12-17T09:32:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"233637752266073219136350640926484661991","date":"2025-12-16T08:13:21+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"149556016268220273694661943328930297083","date":"2025-12-15T21:33:59+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-24T20:21:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"303850935914467573599869399799200689310","date":"2025-11-21T10:20:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"192684149239879341413934372993296144708","date":"2025-11-19T07:17:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"93944167388770716611737085222575775201","date":"2025-11-19T06:25:33+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-13T10:29:22+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-13T10:08:29+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-11T17:18:58+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-08T07:11:16+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-11-08T07:08:41+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d1d2d8ee-f130-4f2b-9b0a-de155738bf47","owner":[],"postedDate":"November 26th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":58536669,"name":"Health sciences/Biomarkers"},{"id":58536670,"name":"Health sciences/Diseases"},{"id":58536671,"name":"Biological sciences/Immunology"},{"id":58536672,"name":"Health sciences/Medical research"},{"id":58536673,"name":"Health sciences/Rheumatology"}],"tags":[],"updatedAt":"2026-03-16T16:05:14+00:00","versionOfRecord":{"articleIdentity":"rs-7950771","link":"https://doi.org/10.1038/s41598-026-44125-z","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-03-13 15:58:55","publishedOnDateReadable":"March 13th, 2026"},"versionCreatedAt":"2025-11-26 06:30:27","video":"","vorDoi":"10.1038/s41598-026-44125-z","vorDoiUrl":"https://doi.org/10.1038/s41598-026-44125-z","workflowStages":[]},"version":"v1","identity":"rs-7950771","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7950771","identity":"rs-7950771","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}