REVIEW – June 2004

Cyclic citrullinated peptide antibodies in rheumatoid arthritis

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Abstract

Rheumatoid arthritis (RA) is the most common autoimmune rheumatic disease. It is characterized by inflammation of the synovial membrane of the diarthroidal joints. The diagnosis of RA is primarily based on clinical symptoms. Serological diagnosis has been limited. The rheumatoid factor (RF), which is the most frequently tested serological marker, is not very specific for RA. Recently a new serological test, the anti-cyclic citrullinated peptide (anti-CCP) ELISA (enzyme linked immunosorbent assay) was developed and it has excellent specifity for the diagnosis of RA, especially in patients with early disease. Using several citrulline-containing peptide variants in ELISA, autoantibodies could be detected in 76% of RA sera with a specifity of 97%. Citrulline is an unusual amino acid resulting from an enzymatically posttranslationally modified arginine residue. Citrulline is present on a few human proteins and anti-CCP antibodies are locally generated in the inflamed joint. Local citrullination of extravascular proteins might be one of the initiating events leading to autoimmunity of RA. Several studys have shown that anti-CCP antibodies have significant prognostic utility in determing damage in early RA. Anti-CCP positive patients develop more severe damage in early RA, as detected by radiologic investigations, than patients who are anti-CCP negative. Thus these antibodies are very helpful in diagnosing early RA and in deciding whether the patient needs more agressive therapy or not.