AUTOANTIBODIES IN A MULTIINSTITUTIONAL INDIAN INCEPTION COHORT (INSPIRE): PREVALENCE, CLUSTER ANALYSIS AND PHENOTYPE ASSOCIATION

PV189a / #296 Poster Topic: AS22 - SLE Heterogeneity Background/Purpose In SLE the prevalence of autoantibodies is variable across different ethnic group and data on Indian population is limited. Thus, we assessed the prevalence and association of different autoantibody clusters with clinical features in an Indian SLE inception cohort for research. Methods INSPIRE cohort is a cohort with 2503 patients accrued till October 2022 and currently 6 monthly follow-up is ongoing. At inclusion antibodies were assayed using Immunoline (Euroimmune, Germany) or ELISA. To determine autoantibody clusters, an unsupervised random forest algorithm was built with 10000 trees and the resulting proximity matrix was used to generate a distance matrix between individual autoantibodies. Odds ratios were used to identify associations between autoantibody/autoantibody clusters and clinical manifestations. Results A total of 2503 patients (mean age 27.69±10.19 years, 2292 [91.57%] females) were enrolled in the cohort. At the baseline, organ involvement (%) was as follows: constitutional features (68.23), alopecia (77.82), oral ulcers (49.74), acute cutaneous lupus (59.41), subacute/discoid lupus (12.4), arthritis (68.27), pleural effusion (20.94), pericarditis (12.39), nephritis as per active sediments and/or proteinuria (41.23), delirium (1.31), psychosis (2.27), seizures (7.39), autoimmune haemolysis (14.54), leukopenia (31.2), thrombocytopenia (24.85). Proliferative nephritis (class III, IV or combination of III/IV and V) was seen in 396, and non-proliferative lupus nephritis in 235. The median SLEDAI at baseline was 12 (IQR 6-18). Antibodies to the DNA nucleosome complex were the most common with anti-dsDNA in 70.19%, anti-nucleosome in 42.02% and anti-histone in 35.6%. This was followed by antibodies to the ribonuclear complex with anti-Sm (32.16%), anti-RNP (52.01%), anti-Ro52 (37.95%), anti-Ro60 (42.14%) and anti-La (12.26%). Other positive antibodies included anti-Ribosomal P (32.16%), anti-AMA-M2 (8.35%), anti-Scl70 (2.83%) anti-PCNA (4.55%), anti-PM/Scl (2.16%), anti-CENP-B (1.48%) and anti Jo-1 (0.99%). IgG autoantibodies (>40 GPL) to anticardiolipin and β2 glycoprotein1 were present in (10.06%) and (8.4%) patients respectively and 8.86% had lupus anticoagulant. Antibodies to dsDNA, histones and nucleosomes showed association with proliferative nephritis, oral ulcers and arthritis, anti-Ro antibodies had association with alopecia and serositis, antibodies to Sm, RNP and Ribosomal P showed association with mucocutaneous disease. Antibodies to Sm, nRNP, Ro and La were protective for proliferative nephritis. Four clusters of autoantibodies were identified. Cluster 1 had antibodies to dsDNA, histone and nucleosome and accounted for 932 (45.84%) patients. Cluster 2 had antibodies to Sm, nRNP, Ro52, Ro60 and Ribosomal P and accounted for 989 (48.65%) patients. Cluster 3 had autoantibodies to cardiolipin, β2GP1, lupus anticoagulant, La as well as AMA-M2 and accounted for 98 (4.62%) patients. Cluster 4 was a predominantly negative cluster which included antibodies to Scl-70, Jo-1, PCNA, PM-SCL and CENP-B and accounted for 18 (0.89 %) patients. Cluster 1 was associated (odds ratio) with clinically significant proteinuria (1.54) and proliferative lupus nephritis (2.06), pleural effusion (1.29), leukopenia (1.37) and with reduced risk of pericarditis (0.72). Cluster 2 was associated with increased seizures (1.36) and pericarditis (1.52) as well as lower risk of proteinuria (0.74), proliferative nephritis (0.56), leukopenia (0.82) and thrombocytopenia (0.78). Cluster 3 was associated with lower risk of proteinuria (0.57), proliferative nephritis (0.36), pleural effusion (0.41) and leukopenia (0.52). Conclusions The prevalence of anti-Sm and Ribosomal P antibodies is higher in Indian population, and they show association with mucocutaneous disease. While antibodies and Cluster 1 associated with DNA had an association with nephritis. Acknowledgment: The study was funded by a grant from the Department of Biotechnology.