Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.
Autoantibodies to five aminoacyl-tRNA synthetases have been reported, and all have been associated with a syndrome of myositis and interstitial lung disease. Four of these synthetases exist free in the cytoplasm, but the fifth, isoleucyl-tRNA synthetase (recognized by anti-OJ autoantibodies), is a component of the multi-enzyme complex containing at least seven synthetases. In an effort to better understand the origins of these antibodies, we examined sera from 11 patients with anti-OJ autoantibodies for evidence of reaction with other components of the complex. All sera showed a characteristic pattern of 10 proteins bands by immunoprecipitation from HeLa cell extract. 10 of 11 sera significantly inhibited isoleucyl-tRNA synthetase enzyme activity. Serum and IgG from four patients also inhibited leucyl-tRNA synthetase activity, and serum and IgG from two inhibited lysyl-tRNA synthetase. Immunoblotting experiments supported reaction of the two sera with lysyl-tRNA synthetase, and revealed additional reactivity of three sera with a 160-kD component believed to be glutaminyl-tRNA synthetase. Despite reaction of some sera with additional synthetases, the immunoprecipitated tRNA appeared the same with all sera, and functioned as tRNA(ile). While reaction with more than one synthetase was seen with some anti-OJ sera, all synthetases targeted by anti-OJ sera were components of the complex, rather than unassociated synthetases. These findings suggest that an initial autoantibody response against isoleucyl-tRNA synthetase was followed by extension to involve other components of the synthetase complex. These observations may have implications for understanding the generation of antisynthetase autoantibodies.
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
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IN
Targoff
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EP
Trieu
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FW
Miller
D000328:Adult; D000368:Aged; D000596:Amino Acids / Q000378:metabolism; D000604:Amino Acyl-tRNA Synthetases / Q000187:drug effects / Q000276:immunology*; D000918:Antibody Specificity; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001327:Autoimmune Diseases / Q000276:immunology*; D003882:Dermatomyositis / Q000276:immunology; D005260:Female; D006801:Humans; D007533:Isoleucine-tRNA Ligase / Q000187:drug effects / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009097:Multienzyme Complexes / Q000276:immunology*; D009220:Myositis / Q000276:immunology; D017285:Polymyositis / Q000276:immunology; D011233:Precipitin Tests; D011658:Pulmonary Fibrosis / Q000276:immunology; D012343:RNA, Transfer / Q000378:metabolism; D013577:Syndrome
D000596:Amino Acids; D001323:Autoantibodies; D009097:Multienzyme Complexes; D012343:RNA, Transfer; D000604:Amino Acyl-tRNA Synthetases; D007533:Isoleucine-tRNA Ligase