SAT0022 Epigenome-wide association study of rheumatoid arthritis identifies differentially methylated loci in b cells

Background Epigenetic regulation of immune cell types could be critical for the development and maintenance of autoimmune diseases like Rheumatoid Arthritis (RA). B cells are highly relevant in RA, since patients express autoantibodies and depleting this cell type is a successful therapeutic approach. Epigenetic variation, such as DNA methylation, may mediate the pathogenic activity of B cells. Objectives In this study, we performed an epigenome-wide association study (EWAS) for RA with three different replication cohorts, to identify disease-specific alterations in DNA methylation in B cells. Methods Genomic methylation in isolated B lymphocytes was assayed on the Illumina HumanMethylation450 BeadChip, assaying >450,000 different CpG sites. Differential methylated positions (DMPs) were identified in a discovery cohort using a single-point analysis using logistic regression, as well as a pathway-level analysis using a newly developed permutation-based method. A discovery cohort of 50 RA patients and 75 healthy controls from Spain was used to identify the most differentially methylated regions after multiple test correction. Using an independent sample of 15 patients and 15 controls from the same population we performed a replication analysis of the most significant CpG sites and pathways. Using an additional case-control sample of 24 individuals from the UK we provided further evidence of association of the DMPs with RA. Finally, in silico datta from a cohort of systemic lupus erythematosus patients (SLE, n=47) and controls (n=56) from the US, we tested the association of the associated DMPs. Results A total of 64 CpG sites were found to be differentially methylated in RA patients compared to controls in the discovery stage after multiple test correction (q Conclusions Our results highlight genes that may drive the pathogenic activity of B cells in RA and suggest shared methylation patterns with SLE. Disclosure of Interest None declared