Arthritis provoked by linked T and B cell recognition of a glycolytic enzyme.
The hallmark of rheumatoid arthritis (RA) is specific destruction of the synovial joints. In a mouse line that spontaneously develops a disorder with many of the features of human RA, disease is initiated by T cell recognition of a ubiquitously expressed self-antigen; once initiated, pathology is driven almost entirely by immunoglobulins. In this study, the target of both the initiating T cells and pathogenic immunoglobulins was identified as glucose-6-phosphate isomerase, a glycolytic enzyme. Thus, some forms of RA or related arthritides may develop by a mechanism fundamentally different from the currently popular paradigm of a joint-specific T cell response.
Matsumoto
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I
Institut de Génétique et de Biologie Moléculaire et Cellulaire (CNRS/INSERM/ULP), BP 163, 67404 Illkirch, C.U. de Strasbourg, France.
Staub
A
A
Benoist
C
C
Mathis
D
D
D000818:Animals; D017951:Antigen Presentation; D000936:Antigen-Antibody Complex / Q000276:immunology / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003429:Cross Reactions; D004195:Disease Models, Animal; D005956:Glucose-6-Phosphate Isomerase / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology; D007596:Joints / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D011993:Recombinant Fusion Proteins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D001324:Autoantigens; D007136:Immunoglobulins; D011993:Recombinant Fusion Proteins; D005956:Glucose-6-Phosphate Isomerase