New autoantibodies recognized for rheumatoid arthritis

Rheumatoid arthritis has long been associated diagnostically with rheumatoid factor (RF) and anticyclic citrullinated peptide (anti-CCP) autoantibodies. A paper just published in the journal Joint Bone Spine reports on the recognition of additional antibodies to post-translational proteins that are significant for understanding pathophysiological mechanisms in rheumatoid arthritis. The authors first note:

"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."

These modified self-proteins can be targets for inflammation when there is loss of immune tolerance.

"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."

Reactions to oxidized collagen in rheumatoid arthritis

Proteins and other molecules damaged by oxidation can elicit an inflammatory response, highlighting the importance of preventing excessive oxidative stress.

"Finally, the development of antibodies to oxidized type II collagen reflects immunization against collagen modified by oxidation in relation to intraarticular oxidative stress."

This brings to mind the role of oxidized LDL (oxLDL) in vascular inflammatory lesions in cardiovascular disease. The authors conclude:

"These new autoantibodies are both sensitive and specific and may therefore serve as early disease markers and as useful tools for therapeutic monitoring."

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