Since aggressive therapy given early in the rheumatoid arthritis (RA) disease course has the greatest therapeutic potential, early diagnostic tests with both high specificity and sensitivity are desirable. Rheumatoid sera were found to contain antibodies against citrullinated peptides, which are considered to be highly specific markers of RA. In the present work several analogues of the alpha- and beta-chains of fibrin peptides containing different degrees of citrullination have been synthesized and analyzed by ELISA using 111 sera from RA patients. In addition, we have also investigated the synergistic effects of different presentation formats of the synthetic constructs. We have designed chimeric and cyclic peptides that bear different peptide sequences within the same molecule. Our results indicate that the synthesis of peptides bearing fibrinogen and filaggrin domains could be a robust method for the design of useful diagnostic strategies in RA.