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自身免疫性甲状腺疾病中的抗微管蛋白抗体。

Anti-tubulin antibodies in autoimmune thyroid disorders.

作者信息

Rousset B, Bernier-Valentin F, Poncet C, Orgiazzi J, Madec A M, Monier J C, Mornex R

出版信息

Clin Exp Immunol. 1983 May;52(2):325-32.

Abstract

The presence of circulating antibodies directed against a cytoskeletal element, microtubules, in patients with autoimmune thyroid disorders, has been studied using pure brain tubulin as antigen. Immune complexes were immunoprecipitated using a goat anti-human immunoglobulin antibody. Twenty sera among 48 (41%) from patients with Graves' disease and nine sera among 16 (56%) from patients with Hashimoto's thyroiditis had increased levels of anti-tubulin antibodies as compared to that of 26 sera from control subjects. Only one serum among 11 from patients with toxic adenoma was positive. Very similar results were obtained using protein A adsorbent to collect immune complexes. Specificity of the tubulin binding activity was ascertained by dilution of the sera and displacement of tracer tubulin by unlabelled pure tubulin from rat or human brain. Anti-tubulin antibody titres were variable; one serum was positive at dilution higher than 1:15,000, a titre similar to those obtained in animals experimentally immunized against tubulin. Binding of labelled and unlabelled tubulin to immunoglobulins from positive sera was strictly competitive. The apparent affinity constant for the binding of tubulin to human anti-tubulin autoantibodies determined on four sera was 0.2-0.6 X 10(9)/M. There was no significant association between anti-tubulin antibodies and anti-microsomal antibodies or anti-thyroglobulin antibodies or thyroid stimulating antibodies. In contrast, only five to six per cent of sera from patients with other autoimmune diseases: lupus erythematosis or pernicious anaemia, had increased levels of anti-tubulin antibodies. In conclusion, tubulin represents a new autoantigen which is expressed rather specifically in autoimmune thyroid disorders and probably independently from the classical thyroid antigens.

摘要

以纯脑微管蛋白作为抗原,对自身免疫性甲状腺疾病患者体内针对细胞骨架成分微管的循环抗体进行了研究。使用山羊抗人免疫球蛋白抗体对免疫复合物进行免疫沉淀。与26名对照受试者的血清相比,48名格雷夫斯病患者中的20份血清(41%)以及16名桥本甲状腺炎患者中的9份血清(56%)抗微管蛋白抗体水平升高。毒性腺瘤患者的11份血清中只有1份呈阳性。使用蛋白A吸附剂收集免疫复合物也得到了非常相似的结果。通过稀释血清以及用大鼠或人脑来源的未标记纯微管蛋白置换示踪微管蛋白来确定微管蛋白结合活性的特异性。抗微管蛋白抗体滴度各不相同;一份血清在高于1:15,000的稀释度时呈阳性,该滴度与在实验中针对微管蛋白免疫的动物所获得的滴度相似。标记和未标记的微管蛋白与阳性血清中的免疫球蛋白的结合具有严格的竞争性。在四份血清上测定的微管蛋白与人抗微管蛋白自身抗体结合的表观亲和常数为0.2 - 0.6×10⁹/M。抗微管蛋白抗体与抗微粒体抗体、抗甲状腺球蛋白抗体或甲状腺刺激抗体之间没有显著关联。相比之下,其他自身免疫性疾病(如红斑狼疮或恶性贫血)患者的血清中只有5%至6%的抗微管蛋白抗体水平升高。总之,微管蛋白代表一种新的自身抗原,它在自身免疫性甲状腺疾病中特异性表达,可能独立于经典的甲状腺抗原。

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