Figure 2.

Schematic illustration of roles of posttranslational modifications (PTMs) and anti-modified protein antibodies (AMPAs) in rheumatoid arthritis (RA) pathogenesis. Citrullination, carbamylation, and acetylation self-modify proteins to generate autoantigenicity. Autoantigens induce the production of AMPAs. In pre-clinical stage of RA, the production of AMPAs is accompanied by the remodeling of antibodies. Simultaneously, AMPAs interact with other pathogenic factors of RA and undergoes isotype switching. Remodeling of autoantibodies lower the avidity of AMPAs, paradoxically heightening autoimmunogenicity. Titer and diversity of AMPAs gradually increase, driving the development of RA. All values in the graph are qualitative. Abbreviations: PAD, peptidylarginine deiminase; PPAD, PAD of Porphyromonas gingivalis; MPO, myeloperoxidase; LTH, leukotoxic hypercitrullination; Ab, antibody; Ag, antigen; AutoAb, autoantibody. Created with Biorender.com.