Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes joint 
inflammation and extra-articular manifestations. To prevent progressive and 
irreversible structural damage, early diagnosis of RA is of paramount 
importance. Antibodies directed against citrullinated proteins and peptides 
(ACPAs) are the most specific serological markers available for diagnosing RA. 
ACPAs may be detected several years before symptoms appear, and their presence 
at disease onset is a good predictor of the development of erosive joint 
lesions. 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. They give 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. We have recently 
obtained and highlighted the application of chimeric peptides bearing different 
citrullinated protein domains for the design of RA diagnosis systems. Our 
results 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.