m6A RNA-binding Protein as a Novel Autoantigen in Rheumatoid Arthritis 2250120

Abstract

Abstract Introduction Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial inflammation and joint destruction. While several autoantigens have been implicated in RA, the role of m6A RNA modifications in autoimmunity remains unclear. Here, we identify the m6A RNA-binding protein as a novel autoantigen in RA. Methods Immunoprecipitation followed by Western blot revealed a distinct 63-kDa protein in RA patient serum but not in healthy controls. Both a monoclonal antibody (BR2) against the m6A RNA-binding protein and a commercial antibody showed strong immunostaining in RA synovium, particularly in fibroblast-like synoviocytes (FLS). Confocal microscopy confirmed colocalization of BR2 with the commercial antibody. Results The protein was also detected in RA synovial fluid by ELISA. Functionally, siRNA knockdown of the m6A RNA-binding protein, as well as treatment with BR2, reduced expression of proinflammatory mediators including TNF-α, IL-6, MMP-1, and MMP-3. Conclusion These results suggest that the m6A RNA-binding protein contributes to RA pathogenesis and may serve as both a biomarker and a potential therapeutic target. Funding Source (NSTC113-2622-B-039-002) Topic Categories Basic Autoimmunity (BA)