Systemic Inflammation and Lymphocyte Activation Precede Rheumatoid Arthritis

The Allen Institute for Immunology-University of California, San Diego-University of Colorado Transition to Rheumatoid Arthritis (ALTRA) project is a prospective longitudinal cohort study to understand the pre-clinical development of rheumatoid arthritis (RA). We performed cross-sectional and longitudinal multi-omics analyses of peripheral immunity in the anti-citrullinated protein autoantibody-positive (ACPA+) at-risk for RA period. We provide FASTQ files from (1) single-cell RNA sequencing (scRNA-seq) of ACPA+ at-risk (n=45), ACPA+ early RA (n=11), and site-matched ACPA- controls (n=38); (2) scRNA-seq of longitudinal samples from ACPA+ at-risk who developed clinically active RA during our study (n=16 participants, n=75 samples) and ACPA- controls (n=29 subjects, n=89 samples); (3) trimodal TEA-seq of a subset of ACPA+ at-risk (n=7) and ACPA- controls (n=5). Using these data, we characterize pathogenesis prior to clinical RA diagnosis and suggest the at-risk state exhibits substantial immune alterations that could potentially be targeted for early intervention to delay or prevent autoimmunity.]]>
ACPA+ At-risk individuals (ARI): Anti-CCP3 (cyclic citrullinated peptide, 3rd generation test) positive with no history of or examination evidence of synovitis. Exclusions included use of immunomodulatory therapy other than short courses of corticosteroids for non-inflammatory arthritis conditions.ACPA- healthy controls (HC1, HC2): Anti-CCP3 negative with no history or evidence of inflammatory arthritis. HC1 recruited at UCSD, CU. HC2 recruited at Benaroya Research Institute and had additional exclusions of no history of autoimmune or chronic disease.ACPA+ early RA (ERA): Anti-CCP3 positive with greater than or equal to one swollen joint consistent with synovitis. Initial study visit must have taken place within one year of initial diagnosis of synovitis.]]>