Clinical Information

Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic joint inflammation that ultimately leads to joint destruction. RA affects approximately 1% of the world's population. The diagnosis of RA is established primarily on clinical criteria and serologic findings. Historically, rheumatoid factor (RF), which is an antibody specific for the Fc portion of human IgG, has been considered a marker for RA. RF is, in fact, one of the diagnostic criteria for RA that was established by the American College of Rheumatology.(1) Although 50% to 90% of patients with RA are RF-positive, the specificity of the RF test is known to be relatively poor. RF is found in many patients with other autoimmune diseases, infectious diseases and some healthy individuals. Consequently, a search for better diagnostic markers, with improved specificity for RA, ensued. Antiperinuclear factor (APF) and antikeratin antibodies (AKA), identified by immunofluorescence, were found to have a specificity of close to 90% for RA, but testing for these autoantibodies has never become popular. It was subsequently determined that APF and AKA react with the same antigen, specifically a citrullinated form of filaggrin (citrulline is an unusual amino acid formed by posttranslational modification of arginine residues by the enzyme peptidyl arginine deaminase).(2) Recombinant filaggrin fragments, after enzymatic deamination in vitro, react with autoantibodies in RA sera. Synthetic cyclic citrullinated peptide (CCP) variants also react with anti-filaggrin autoantibodies and serve as the substrate for detecting anti-CCP antibodies serologically. Most studies of anti-CCP antibodies demonstrated that these autoantibodies have much improved specificity for RA compared to RF.(3)   

See Connective Tissue Diseases Cascade (CTDC) in Special Instructions; also see Optimized Laboratory Testing for Connective Tissue Diseases in Primary Care: The Mayo Connective Tissue Diseases Cascade in Publications.