Ohara RA, et al. - Through a cohort study of 27 rheumatoid arthritis (RA) patients who were recruited from 2009–2012, the researchers investigated the intrinsic role of inhibitor of DNA binding 1 (ID-1, used to regulate cell growth and differentiation via selective binding and sequestering of distinct transcription factors) in RA fibroblast-like synoviocytes (FLS) and to examine whether ID-1 is citrullinated and autoantigenic in RA. Serum ID-1 levels of RA patients were measured pre- and post-infliximab treatment. Reduction in the serum ID-1 levels with an association with several disease parameters after infliximab treatment was noticed. Diminished growth and a robust elevation in interleukin-6 and IL-8 production upon the deletion of ID-1 were exhibited by the RA FLS. Citrullinated residues levels in RA synovial fluid (SF) were markedly decreased by ID-1 immunodepletion. Citrullinated ID-1 was discovered in homogenized RA synovial tissue. Anti-citrullinated protein antibodies to in vitro–citrullinated recombinant human ID-1 but not to native ID-1 was exhibited by immunodot blot analyses, in RA peripheral blood (PB) sera and SF and not in normal PB sera. The critical arginines ascertained post-assessment of liquid chromatography-tandem mass spectrometry results and corresponding reactivity in immunodot assays for citrullination sites in ID-1 for autoantigenicity were R33, R52, and R121. Hence, FLS proliferation and cytokine secretion, as well as autoantigenicity following citrullination regulation, were novel roles of ID-1 in RA.