Reaction of anti-OJ autoantibodies with components of the multi-enzyme complex of aminoacyl-tRNA synthetases in addition to isoleucyl-tRNA synthetase.
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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DOI：
10.1172/jci116493
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发表时间：
1993-06
期刊：
影响因子：
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通讯作者：
I. Targoff;E. Trieu;Frederick W. Miller
中科院分区：
文献类型：
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作者：
I. Targoff;E. Trieu;Frederick W. Miller
已报道了针对五种氨酰-tRNA合成酶的自身抗体，并且所有这些抗体都与肌炎和间质性肺病综合征相关。这些合成酶中有四种游离存在于细胞质中，但第五种，异亮氨酰-tRNA合成酶（由抗OJ自身抗体识别），是含有至少七种合成酶的多酶复合物的组成部分。为了更好地了解这些抗体的起源，我们检查了11例抗OJ自身抗体患者的血清，以寻找与复合物其他成分反应的证据。用免疫沉淀法从HeLa细胞提取物中分离出10条特异性蛋白带。11份血清中有10份对异亮氨酰-tRNA合成酶活性有显著抑制作用。4例患者的血清和IgG也抑制亮氨酰-tRNA合成酶活性，2例患者的血清和IgG抑制赖氨酰-tRNA合成酶。免疫印迹实验支持反应的两个血清与赖氨酰-tRNA合成酶，并揭示了额外的反应性的三个血清与160-kD的组件被认为是氨酰-tRNA合成酶。尽管一些血清与另外的合成酶反应，但免疫沉淀的tRNA似乎与所有血清相同，并且作为tRNA（ile）起作用。虽然与一个以上的合成酶的反应，看到一些抗OJ血清，所有合成酶的抗OJ血清的目标是复杂的组件，而不是无关的合成酶。这些发现表明，对异亮氨酰-tRNA合成酶的初始自身抗体反应随后延伸到涉及合成酶复合物的其他组分。这些观察结果可能对理解抗合成酶自身抗体的产生有影响。
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.