Autoimmunity against fibrinogen mediates inflammatory arthritis in mice.
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.
Ho
Peggy P
PP
Department of Neurological and Neurologic Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
Lee
Lowen Y
LY
Zhao
Xiaoyan
X
Tomooka
Beren H
BH
Paniagua
Ricardo T
RT
Sharpe
Orr
O
BenBarak
Maya J
MJ
Chandra
Piyanka E
PE
Hueber
Wolfgang
W
Steinman
Lawrence
L
Robinson
William H
WH
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
D001323:Autoantibodies; D001324:Autoantigens; D005340:Fibrinogen