New autoantibodies associated with rheumatoid arthritis recognize posttranslationally modified self-proteins

Citrullination, carbamylation and oxidation are posttranslational modifications of proteins that produce neoepitopes. Rheumatoid arthritis (RA) is an autoimmune disease of which one distinctive feature is the development of B-cell-mediated immunity against these neoepitopes. Antibodies to citrullinated proteins (ACPAs) were identified nearly two decades ago and are now widely used in clinical practice. The identification of additional citrullinated proteins as potential autoantibody targets has suggested new pathophysiological hypotheses and prompted studies of potential associations with disease severity or specific disease patterns. Carbamylation is a nonenzymatic posttranslational modification that produces homocitrullines, against which newly identified autoantibodies different from ACPAs have been found in over 15% of patients with RA. Finally, the development of antibodies to oxidized type II collagen reflects immunization against collagen modified by oxidation in relation to intraarticular oxidative stress. These new autoantibodies are both sensitive and specific and may therefore serve as early disease markers and as useful tools for therapeutic monitoring.