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The Journal of Immunology, 2005, 174: 5057-5064.
Copyright © 2005 by The American Association of Immunologists

Fibrin Deimination in Synovial Tissue Is Not Specific for Rheumatoid Arthritis but Commonly Occurs during Synovitides1

Sabine Chapuy-Regaud*, Mireille Sebbag*, Dominique Baeten{dagger}, Cyril Clavel*, Céline Foulquier*, Filip De Keyser{dagger} and Guy Serre2,*

* Laboratory of Epidermis Differentiation and Rheumatoid Autoimmunity, Unité Mixte de Recherche 5165 Centre National de la Recherche Scientifique-Toulouse III University, Institut Fédératif de Recherche 30 (Centre National de la Recherche Scientifique-Institut National de la Santé et de la Recherche Médicale-Université Paul Sabatier-Centre Hospitalier Universitaire de Toulouse), Toulouse, France; and {dagger} Department of Rheumatology, Ghent University Hospital, Ghent University, Ghent, Belgium

Autoantibodies to deiminated (citrullinated) proteins are the most specific serological markers of rheumatoid arthritis (RA). Deimination is critical in generating the peptidic epitopes they recognize. In the synovial tissue (ST), deiminated forms of the {alpha}- and {beta}-chains of fibrin are their major autoantigenic targets (anti-human fibrin(ogen) autoantibodies (AhFibA)). We investigated whether the presence of deiminated fibrin in the ST was specific for RA, because this could explain why AhFibA are RA specific. In 13 patients with RA and 19 patients with various other rheumatological disorders, knee ST biopsies were collected in macroscopically inflamed areas identified under arthroscopy. Synovitis was histopathologically confirmed in all of the biopsies. By immunoblotting, using antisera to fibrin, Abs to citrullyl residues, and AhFibA purified from RA sera, deiminated fibrin was evidenced in ST extracts from all of the patients. Moreover, variations in the degree of fibrin deimination were observed that were not related to the disease. Immunohistochemical analysis, using Abs to citrullyl residues and an antiserum to fibrin on adjacent serial sections of ST, confirmed the results because deiminated proteins colocalized with fibrin in RA as well as in control patients. Therefore, fibrin deimination in the ST is a general phenomenon associated to any synovitis, which does not necessarily induce a B autoimmune response with production of AhFibA.




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