Identification of novel citrullinated antigens in rheumatoid arthritis (RA) and the role of anti-CCP antibody in the pathogenesis of RA

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Anti-CCP (cyclic citrullinated peptides) antibody has been demonstrated to be a useful serological marker for early diagnosis as well as prediction of joint destruction of rheumatoid arthritis (RA). However, the role of anti-CCP antibody in the pathogenesis of RA has not been established. Thus it is not known whether anti-CCP is produced as a result of rheumatoid synovitis and whether cirtrullination of putative autoantigens by peptidylarginine deiminases (PADIs) and subsequent induction of anti-CCP antibody is involved for the joint destruction in RA. So far, citrullinated forms of fibrinogen, filaggrin, vimentin have been implicated as putative autoantigens in RA. However, the specific presence of such citrullinated antigens in rheumatoid synovium has remained to be elucidated.In this study we established a brand-new ELISA system to detect anti-citrullinated peptide antibody using citrullinated form of rheumatoid synovial cell lysate, recombinant p53 and synthetic fibrinogen peptide. Although the sensitivity of the present ELISA system was inferior to the commercially available anti-CCP2 kit, it was possible to classify RA patients according to the results of our anti-citrullinated peptide antibodies. We also identified citrullinated peptides as a protamine-binding fraction of synovial fluids from RA patients. We further identified citrullinated form of fibrinogen specifically in rheumatoid synovial fluids. Further studies examining biochemical and immunological nature of the citrullinated antigens that we have identified and their immunogenicity would be warranted for elucidation of the pathogenesis of RA.