Diagnostic value of anti-human citrullinated fibrinogen ELISA and comparison with four other anti-citrullinated protein assays

Clinical indicators of rheumatoid arthritis (RA) are pain and swelling of the proximal interphalangeal and metacarpophalangeal joints. Larger joints such as knee, elbow and ankle joints may also be affected. Synovial inflammation and joint destruction together with the extra-articular manifestations of the disease are responsible for a severe decline in the RA patient's quality of life. It is important to identify RA early. Joint erosions, which are irreversible, occur early in the disease process and intervention with aggressive therapy is most successful if it is applied early in the disease course [1]. A sensitive and specific serological test is needed for application in this window in the disease course, when often not all clinical manifestations are apparent.Several autoantibody systems have been described in this autoimmune disease [2]. The presence of the rheumatoid factor (RF), directed against the Fc part of an IgG molecule, is one of the American College of Rheumatology (ACR) criteria for RA [3]. This antibody is present in about 65–75% of RA patients. However, because it is also found in patients with other autoimmune diseases or infectious diseases, and even in the healthy elderly, it has limited specificity. The presence of anti-citrullinated protein/peptide antibodies (ACPAs), on the other hand, is significantly more specific for RA. ACPAs are directed against various proteins that have one trait in common; some of their arginines have been converted to citrulline by post-translational modification, catalyzed by peptidylarginine deiminase enzymes [4,5].Depending on the substrate, various assays for detection of ACPAs have been developed. Human buccal mucosa cells and rat oesophagus provide the antigenic substrate for anti-perinuclear factor and anti-keratin antibodies [6,7]. The difficulty in standardizing these natural substrates, together with arbitrary interpretation of the indirect immunofluorescence pattern, has hampered the widespread use of the