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Citations to this article

Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.
I N Targoff, … , E P Trieu, F W Miller
I N Targoff, … , E P Trieu, F W Miller
Published June 1, 1993
Citation Information: J Clin Invest. 1993;91(6):2556-2564. https://doi.org/10.1172/JCI116493.
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Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.

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Abstract

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.

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I N Targoff, E P Trieu, F W Miller

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Molecular analysis of a major antigenic region of the 240-kD protein of Mi-2 autoantigen
Q Ge, DS Nilasena, CA O'Brien, MB Frank, IN Targoff
Journal of Clinical Investigation 1995
Autoantibodies in the diagnosis of systemicrheumatic diseases
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RC Nichols, N Raben, CF Boerkoel, PH Plotz
Gene 1995
Analysis of the mi-2 autoantigen of dermatomyositis
DS Nilasena, EP Trieu, IN Targoff
Arthritis & Rheumatism 1995
An immunodominant antigen of Brugia malayi is an asparaginyl-tRNA synthetase
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Analysis of the specificity of anti-pm-scl autoantibodies
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Arthritis & Rheumatism 1994
IMMUNE MANIFESTATIONS OF INFLAMMATORY MUSCLE DISEASE
IN Targoff
Rheumatic diseases clinics of North America 1994
Primary structure and functional expression of human Glycyl-tRNA synthetase, an autoantigen in myositis
Q Ge, EP Trieu, IN Targoff
The Journal of biological chemistry 1994
A motif in human histidyl-tRNA synthetase which is shared among several aminoacyl-tRNA synthetases is a coiled-coil that is essential for enzymatic activity and contains the major autoantigenic epitope
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Referenced in 8 patents
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