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Anti-citrullinated protein auto-antibodies : diagnosis and specific immunotherapy
Our group is involved in the study of the rheumatoid arthritis (RA)-specific autoantibodies directed to citrullinated proteins (ACPAs). ACPAs have a high diagnostic value. They are present in up to 80% of sera from RA-patients with a specificity > 98%.
Our laboratory has largely contributed to the characterization of the antigenic targets of ACPAs. In 2001, we identified citrullinated forms of the α- and β-chains of fibrin as major targets of ACPA in the synovial tissue of RA patients. However, several other citrullinated proteins have been shown to be reactive with ACPA in vitro and some of them have been proposed as possible in vivo targets. Our current work aims to demonstrate that there is only one family of ACPA, that their major antigenic target corresponds to citrullinated forms of fibrin and that these autoantibodies variously crossreact with other citrullinated proteins depending on the considered patient serum.
More recently, we identified two peptides α36-50 and β60-74 as bearing the immunodominant epitopes of citrullinated fibrin. Then, we defined three 4- and 5-amino acid-long minimal epitopes that together almost entirely encompass the reactivity of ACPA to citrullinated fibrin for a vast majority of RA-sera. We underwent to develop tests for the detection of each subfamily of ACPA directed to each of those 3 minimal epitopes. These tests will allow to define different groups of patients according to the reactivity of their sera to the 3 minimal epitopes and to evaluate the prognostic value and the predictive value for the response to treatment of ACPA directed to each immunodominant epitope. We are also studying the evolution of the ACPA titer and specificity in response to treatment by anti-CD20 antibodies.
Position of immunoreactive peptides on a schematic ribbon representation of the 3D structure of the fibrinogen molecule
(Eur J Immunol 2006, 36:2250).