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分子模拟是乳糜泻自身免疫反应的可能原因吗?抗麦醇溶蛋白抗体与肠上皮细胞上的表位发生交叉反应。

Molecular mimicry as a possible cause of autoimmune reactions in celiac disease? Antibodies to gliadin cross-react with epitopes on enterocytes.

作者信息

Tucková L, Tlaskalová-Hogenová H, Farré M A, Karská K, Rossmann P, Kolínská J, Kocna P

机构信息

Department of Immunology and Gnotobiology, First Faculty of Medicine, Prague, Czech Republic.

出版信息

Clin Immunol Immunopathol. 1995 Feb;74(2):170-6. doi: 10.1006/clin.1995.1025.

Abstract

Structural similarities between external antigen and self components are believed to be one of the possible causes of autoimmunity. This study describes the presence of similar structures shared by gliadin and enterocyte surface molecules recognized by antigliadin mAbs. The reactivity of mAbs to gliadin was followed by ELISA using fixed enterocytes, their brush-border membranes, or purified enterocyte antigen. The specificity of reaction was confirmed by ELISA inhibition studies and by immunohistochemical staining of rat tissue sections using biotin-avidin-peroxidase technique. Immunoprecipitation analysis of 125I-labeled intestinal epithelial cells using antigliadin mAb revealed the presence of two main cross-reactive molecules of 28 and 62 kDa. The 62-kDa and an associated 66-kDa protein were isolated by affinity chromatography. Immunoblotting analysis showed that a 28-kDa protein detected by immunoprecipitation also reacted with IgA of celiac disease patient sera.

摘要

外部抗原与自身成分之间的结构相似性被认为是自身免疫的可能原因之一。本研究描述了麦醇溶蛋白与抗麦醇溶蛋白单克隆抗体识别的肠上皮细胞表面分子所共有的相似结构的存在。使用固定的肠上皮细胞、其刷状缘膜或纯化的肠上皮细胞抗原,通过酶联免疫吸附测定(ELISA)追踪单克隆抗体与麦醇溶蛋白的反应性。通过ELISA抑制研究以及使用生物素-抗生物素蛋白-过氧化物酶技术对大鼠组织切片进行免疫组织化学染色,证实了反应的特异性。使用抗麦醇溶蛋白单克隆抗体对¹²⁵I标记的肠上皮细胞进行免疫沉淀分析,结果显示存在两种主要的交叉反应分子,分子量分别为28 kDa和62 kDa。通过亲和层析分离出了62 kDa和一种相关的66 kDa蛋白质。免疫印迹分析表明,通过免疫沉淀检测到的28 kDa蛋白质也与乳糜泻患者血清中的IgA发生反应。

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