Targoff I N, Trieu E P, Miller F W
Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
J Clin Invest. 1993 Jun;91(6):2556-64. doi: 10.1172/JCI116493.
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.
据报道，存在针对五种氨酰 - tRNA合成酶的自身抗体，且所有这些自身抗体都与肌炎和间质性肺病综合征相关。其中四种合成酶游离于细胞质中，但第五种，异亮氨酰 - tRNA合成酶（可被抗OJ自身抗体识别）是包含至少七种合成酶的多酶复合物的一个组成部分。为了更好地理解这些抗体的起源，我们检测了11例抗OJ自身抗体患者的血清，以寻找与该复合物其他成分发生反应的证据。通过对HeLa细胞提取物进行免疫沉淀，所有血清均显示出10条蛋白带的特征模式。11份血清中有10份显著抑制异亮氨酰 - tRNA合成酶的酶活性。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合成酶活性。免疫印迹实验支持两份血清与赖氨酰 - tRNA合成酶发生反应，并揭示三份血清与一种被认为是谷氨酰胺酰 - tRNA合成酶的160-kD成分存在额外的反应性。尽管一些血清与其他合成酶发生了反应，但所有血清免疫沉淀的tRNA看起来相同，并且发挥tRNA(ile)的功能。虽然一些抗OJ血清与不止一种合成酶发生反应，但抗OJ血清靶向的所有合成酶都是该复合物的成分，而非未结合的合成酶。这些发现表明，最初针对异亮氨酰 - tRNA合成酶的自身抗体反应随后扩展至涉及合成酶复合物的其他成分。这些观察结果可能对理解抗合成酶自身抗体的产生具有启示意义。
