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Department of Biology and Pathology of the Cell, Institut National de la Santé et de la Recherche Médicale, Contrat Jeune Formation 96-02, Toulouse-Purpan School of Medicine, University Toulouse III (Institute Fédératif de Recherche 30, Institut National de la Santé et de la Recherche Médicale, Centre National de la Recherche Scientifique, Université Paul Sabatier-Toulouse III, Centre Hospitalier Universitaire), Toulouse, France;
Department of R & D Immunoassays, bioMérieux, Marcy l’Étoile, France; and
Department of Cell Chemistry, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan
Antifilaggrin autoantibodies (AFA) are a population of IgG autoantibodies associated to rheumatoid arthritis (RA), which includes the so-called "antikeratin" Abs and antiperinuclear factor. AFA are the most specific serological markers of RA. We previously showed that they recognize human epidermal filaggrin and other profilaggrin-related proteins of various epithelial tissues. Here, we report further characterization of the protein Ags and epitopes targeted by AFA. All the Ags that exhibit numerous neutral/acidic isoelectric variants were immunochemically demonstrated to be deiminated proteins. In vitro deimination of a recombinant human filaggrin by a peptidylarginine deiminase generated AFA epitopes on the protein. Moreover, two of three filaggrin-derived synthetic peptides with a citrulline in the central position were specifically and widely recognized by AFA affinity-purified from a series of RA sera. These results indicate that citrulline residues are constitutive of the AFA epitopes, but only in the context of specific amino acid sequences of filaggrin. In competition experiments, the two peptides abolished the AFA reactivity of RA sera, showing that they present major AFA epitopes. These data should help in the identification of a putative deiminated AFA-inducing or cross-reactive articular autoantigen and provide new insights into the pathogenesis of RA. They could also open the way toward specific immunosuppressive and/or preventive therapy of RA.
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S Genevay, G Hayem, P Verpillat, and O Meyer An eight year prospective study of outcome prediction by antiperinuclear factor and antikeratin antibodies at onset of rheumatoid arthritis Ann Rheum Dis, August 1, 2002; 61(8): 734 - 736. [Abstract] [Full Text] [PDF]
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R. Fritsch, D. Eselbock, K. Skriner, B. Jahn-Schmid, C. Scheinecker, B. Bohle, M. Tohidast-Akrad, S. Hayer, J. Neumuller, S. Pinol-Roma, et al. Characterization of Autoreactive T Cells to the Autoantigens Heterogeneous Nuclear Ribonucleoprotein A2 (RA33) and Filaggrin in Patients with Rheumatoid Arthritis J. Immunol., July 15, 2002; 169(2): 1068 - 1076. [Abstract] [Full Text] [PDF]
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T Avcin, R Cimaz, F Falcini, F Zulian, G Martini, G Simonini, V Porenta-Besic, G Cecchini, M O Borghi, and P L Meroni Prevalence and clinical significance of anti-cyclic citrullinated peptide antibodies in juvenile idiopathic arthritis Ann Rheum Dis, July 1, 2002; 61(7): 608 - 611. [Abstract] [Full Text] [PDF]
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S. Bas, T. V. Perneger, M. Seitz, J.-M. Tiercy, P. Roux-Lombard, and P. A. Guerne Diagnostic tests for rheumatoid arthritis: comparison of anti-cyclic citrullinated peptide antibodies, anti-keratin antibodies and IgM rheumatoid factors Rheumatology, July 1, 2002; 41(7): 809 - 814. [Abstract] [Full Text] [PDF]
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N. Jonca, M. Guerrin, K. Hadjiolova, C. Caubet, H. Gallinaro, M. Simon, and G. Serre Corneodesmosin, a Component of Epidermal Corneocyte Desmosomes, Displays Homophilic Adhesive Properties J. Biol. Chem., February 8, 2002; 277(7): 5024 - 5029. [Abstract] [Full Text] [PDF]
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L Nogueira, M Sebbag, C Vincent, M Arnaud, B Fournie, A Cantagrel, M Jolivet, and G Serre Performance of two ELISAs for antifilaggrin autoantibodies, using either affinity purified or deiminated recombinant human filaggrin, in the diagnosis of rheumatoid arthritis Ann Rheum Dis, September 1, 2001; 60(9): 882 - 887. [Abstract] [Full Text] [PDF]
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 H. Asaga, K. Nakashima, T. Senshu, A. Ishigami, and M. Yamada Immunocytochemical localization of peptidylarginine deiminase in human eosinophils and neutrophils J. Leukoc. Biol., July 1, 2001; 70(1): 46 - 51. [Abstract] [Full Text] [PDF]
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C. Masson-Bessiere, M. Sebbag, E. Girbal-Neuhauser, L. Nogueira, C. Vincent, T. Senshu, and G. Serre The Major Synovial Targets of the Rheumatoid Arthritis-Specific Antifilaggrin Autoantibodies Are Deiminated Forms of the {{alpha}}- and {{beta}}-Chains of Fibrin J. Immunol., March 15, 2001; 166(6): 4177 - 4184. [Abstract] [Full Text] [PDF]
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 R. B. Presland and B. A. Dale Epithelial Structural Proteins of the Skin and Oral Cavity: Function in Health and Disease Critical Reviews in Oral Biology & Medicine, January 1, 2000; 11(4): 383 - 408. [Abstract] [Full Text] [PDF]
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K. Nakashima, T. Hagiwara, A. Ishigami, S. Nagata, H. Asaga, M. Kuramoto, T. Senshu, and M. Yamada Molecular Characterization of Peptidylarginine Deiminase in HL-60 Cells Induced by Retinoic Acid and 1alpha ,25-Dihydroxyvitamin D3 J. Biol. Chem., September 24, 1999; 274(39): 27786 - 27792. [Abstract] [Full Text] [PDF]
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