Citrullination and rheumatoid arthritis

Abstract Anti-citrullinated peptide antibody (ACPA) is detected in rheumatoid arthritis (RA)patients, and its clinical importance is established for RA diagnosis and as a prognosis marker. ACPA itself plays some roles in RA pathogenesis, such as promoting osteoclastogenesis. Citrullinated epitope-specific T cells also play an important role in RA pathogenesis and a recent study showed the clinical efficacy of tolerance induction of citrullinated epitopes for RA. As a source of citrullinated antigens, neutrophil extracellular traps (NETs)are supposed, because NETs contain a plenty of citrullinated histones. Peptidylarginine deiminase (PADI) 4 is one of the RA risk genes and associated with protein citrullinations. PADI4 plays a pivotal role in NETosis. And, we recently demonstrated its importance in arthritis by analyzing PADI4-deficient mice.