[Anti-cyclic citrullinated peptide antibodies and rheumatoid arthritis]

Rheumatoid arthritis (RA) is a severe, progressive, systemic inflammatory disease of unknown etiology. Early diagnosis of RA is important to identify individuals who will develop severe destructive disease, so that effective treatment can be initiated before irreversible damage occurs. Rheumatoid factor (RF) has been commonly used as a serological marker for RA, although RF had a tolerable sensitivity of 75.9% for RA, but low specificity of 78.7% and 75.4% for patients with other rheumatic diseases and chronic inflammatory disease, respectively. Antibodies to citrullinated protein/peptide antigens, i.e., to peptides post-translationally modified by the conversion of arginine to cilrulline (ACPA), are specific serological markers for RA. Not only did anti-cyclic citrullinated peptide antibody (anti-CCP) demonstrate a higher sensitivity of 78.5% when compared to RF, but anti-CCP also had a much higher specificity of 95.9% and 97.9% for other rheumatic diseases and chronic inflammatory disease patients, respectively. Moreover, meta-analysis revealed that pooled sensitivity and pooled specificity were 67% and 95% for anti-CCP, 69% and 85% for RF, respectively, and that anti-CCP was more specific than RF for diagnosing RA. In 2009, ACPA (anti-CCP) was included in the new Criteria for RA from the American College of Rheumatology and the European League Against Rheumatism. Anti-CCP testing is particularly useful in the diagnosis of RA, being present early in the disease process, and able to predict severe disease and irreversible damage. In addition, the titers might be early predictors of the efficacy of anti-TNF therapy. In this review, we discuss the historical background of anti-CCP as well as its diagnostic performance, usefulness for early diagnosis, prognostic capability, and pathogenesis of RA.