title: Autoimmunity against fibrinogen mediates inflammatory arthritis in mice.
abstract: Rheumatoid arthritis (RA) is an autoimmune synovitis characterized by the presence of anticitrullinated protein Abs, although the exact targets and role of anticitrullinated protein autoimmunity in the pathogenesis of RA remain to be defined. Fibrinogen, which can be citrullinated, has recently emerged as a candidate autoantigen. To determine whether autoimmunity against fibrinogen can mediate inflammatory arthritis, we immunized a variety of common mouse strains with fibrinogen and found that DBA/1 and SJL mice developed an inflammatory and erosive arthritis. Mice with fibrinogen-induced arthritis (FIA) possess fibrinogen-reactive T cells that produce the proinflammatory cytokines IL-6, IL-17, TNF-alpha, and IFN-gamma. FIA can be adoptively transferred with either plasma or fibrinogen-specific T cells from diseased mice. Mice with FIA possess rheumatoid factor, circulating immune complexes, and anticyclic citrullinated peptide Abs, all of which are characteristic of human RA. These observations demonstrate that fibrinogen is arthritogenic in mice and that the pathogenesis of FIA is mediated by both autoantibodies and fibrinogen-reactive T cells.
authors: Department of Neurological and Neurologic Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: Peggy P
authors: PP
authors: Ho
authors: Lowen Y
authors: LY
authors: Lee
authors: Xiaoyan
authors: X
authors: Zhao
authors: Beren H
authors: BH
authors: Tomooka
authors: Ricardo T
authors: RT
authors: Paniagua
authors: Orr
authors: O
authors: Sharpe
authors: Maya J
authors: MJ
authors: BenBarak
authors: Piyanka E
authors: PE
authors: Chandra
authors: Wolfgang
authors: W
authors: Hueber
authors: Lawrence
authors: L
authors: Steinman
authors: William H
authors: WH
authors: Robinson
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000473:pathology; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D005340:Fibrinogen / Q000276:immunology*; D006801:Humans; D013058:Mass Spectrometry; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D005340:Fibrinogen