Clinical significance of anti-CCP antibodies in rheumatoid arthritis

A number of novel autoantibodies have been recently described in rheumatoid arthritis (RA), and their clinical significance and possible pathogenic roles have been discussed. In particular, new autoantibodies to citrullinated proteins such as filaggrin and its circular form (cyclic citrullinated peptide: CCP) are especially noteworthy because of their high sensitivity and high specificity. There are many studies that anti-CCP antibodies may serve as a powerful serologic marker for early diagnosis of RA and prognostic prediction of joint destruction. Anti-citrullinated protein antibodies are locally produced in RA joints, and citrullinated proteins (most are fibrins) are localized in RA synovial tissue. This finding strongly suggests a possibility that local citrullination of intra-articular proteins might be the initial event leading to autoantibody production in RA. Genetic factors such as a gene polymorphism of the citrullinating enzyme, PADI, might be associated with the breakage of self-tolerance and induction of autoimmunity against citrullinated proteins.