Anti-Jo-1 autoantibodies and the immunopathogenesis of autoimmune myositis.
Polymyositis and dermatomyositis are inflammatory myopathies characterized by proximal muscle weakness and myopathic electromyographic and histological findings. While the causes of myositis are not known, the close association of these disorders with a spectrum of autoantibodies suggests an etiologic and/or pathogenetic role for autoimmune processes. Of particular interest in this regard are antibodies directed against histidyl as well as other tRNA synthetases which are almost uniquely associated with myositis and may define a distinct subset of patients. Recently we isolated the histidyl tRNA synthetase gene which encodes the autoantigen representing the most frequent target of the myositis autoimmune response. The isolation and expression of this gene has allowed us to investigate both the autoreactive epitopes on histidyl-tRNA synthetase and the extent to which these correlate with functional epitopes on the molecule. As described here, the results of these studies as well as other recent data pertaining to the immunopathogenesis of myositis, provide a framework for delineating the mechanisms which render synthetases and other translation-related proteins autoantigenic in myositis, and allow one to examine the significance of such autoimmune responses in the etiology and pathogenesis of inflammatory myopathy.
Tsui
F W
FW
Department of Medicine, University of Toronto, Ontario, Canada.
Siminovitch
K A
KA
D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000209:etiology / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D006643:Histidine-tRNA Ligase / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular / Q000276:immunology; D015151:Immunoblotting; D009220:Myositis / Q000209:etiology / Q000276:immunology*; D014780:Viruses / Q000276:immunology
D001323:Autoantibodies; D001324:Autoantigens; D000939:Epitopes; D006643:Histidine-tRNA Ligase