Citrullinated Peptides in the Diagnosis of Rheumatoid Arthritis

Antibodies directed against citrullinated proteins and peptides (ACPAs) are the most specific serological markers available for diagnosing rheumatoid arthritis (RA). ACPAs may be detected several years before symptoms of RA appear, and their presence at disease onset is a good predictor of the development of erosive joint lesions. RA patients can be classified into two major groups: those who have ACPAs and those who do not. The presence of ACPAs at early stages of RA predicts the development of earlier and more widespread joint erosions, and low remission rates. Synthetic peptides can replace cognate proteins in solid-phase assays for specific autoantibody recognition in RA patients. The use of synthetic peptides instead of proteins represents an advantage in terms of the reproducibility of such immunoassays. Proteins also contain non-citrullinated epitopes that are recognized by non-RA sera and this could reduce the specificity of the test. The use of synthetic citrullinated peptides gives absolute control over the exact epitopes presented. Furthermore, it is difficult to prepare sufficient amounts of high-quality antigenic proteins with a well-defined degree of citrullination. Synthetic citrullinated peptides, in contrast, are easily obtained in a pure form with a well-defined chemical structure and the epitopes can be precisely oriented in the plate by covalent binding of the peptides. Chimeric peptides bearing different citrullinated protein domains have recently been used in the design of RA diagnosis systems. The results of the application of those systems indicate that more than one serological test is required to classify RA patients based on the presence or absence of ACPAs. Each of the target molecules reported (fibrin, vimentin and filaggrin) helps to identify a particular subset of RA patients.