Identification of tissue transglutaminase as the autoantigen of celiac disease
Identification of tissue transglutaminase as the autoantigen of celiac disease
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DOI：
10.1038/nm0797-797
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发表时间：
1997-07-01
期刊：
影响因子：
82.9
通讯作者：
Schuppan, D
中科院分区：
文献类型：
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作者：
Dieterich, W;Ehnis, T;Schuppan, D
乳糜泻的特点是小肠损伤，吸收绒毛缺失和隐窝增生，通常导致吸收不良(1)。除了营养缺乏，长期的乳糜泻与恶性肿瘤的风险增加有关，特别是肠t细胞淋巴瘤（1-3）。乳糜泻是由摄入麦胶蛋白引起的，麦胶蛋白是小麦面筋的一种成分，通常在停药后消退。麦胶蛋白引发粘膜损伤，这涉及到具有遗传易感性的个体的免疫过程。然而，导致乳糜泻特有的小肠损伤的机制仍在争论中（4-6）。小肠活检显示无麸质饮食后黏膜变平，被认为是诊断经典乳糜泻的主要方法(7)。此外，针对麦胶蛋白和肌内膜（平滑肌结缔组织的一种结构）的IgA抗体是检测乳糜泻患者和治疗控制的宝贵工具（7-9）。儿童乳糜泻的发病率从西爱尔兰的1:30 00到其他欧洲国家的1:4700(10-12)，通过血清学筛查检测到的亚临床病例显示，意大利和美国的患病率分别为3.3 / 1000和4 / 1000，针对肌内膜的IgA抗体是乳糜泻的特别特异性指标（9,15），这表明该结构含有一种或多种靶自身抗原，在疾病的发病机制中起作用（16,17）。然而，肌内膜自身抗原的鉴定仍然是难以捉摸的。我们将组织转谷氨酰胺酶鉴定为未知的肌内膜自身抗原。有趣的是，麦胶蛋白是这种酶的首选底物，从而产生新的抗原表位。
Celiac disease is characterized by small intestinal damage with loss of absorptive villi and hyperplasia of the crypts, typically leading to malabsorption(1). In addition to nutrient deficiencies, prolonged celiac disease is associated with an increased risk for malignancy, especially intestinal T-cell lymphoma(1-3). Celiac disease is precipitated by ingestion of the protein gliadin, a component of wheat gluten, and usually resolves on its withdrawal. Gliadin initiates mucosal damage which involves an immunological process in individuals with a genetic predisposition. However, the mechanism responsible for the small intestinal damage characteristic of celiac disease is still under debate(4-6). Small intestinal biopsy with the demonstration of a flat mucosa which is reversed on a gluten-free diet is considered the main approach for diagnosis of classical celiac disease(7). In addition, IgA antibodies against gliadin and endomysium, a structure of the smooth muscle connective tissue, are valuable tools for the detection of patients with celiac disease and for therapy control(7-9). Incidence rates of childhood celiac disease range from 1:300 in Western Ireland to 1:4700 in other European countries(10-12), and subclinical cases detected by serological screening revealed prevalences of 3.3 and 4 per 1000 in Italy and the USA, respectively IgA antibodies to endomysium are particularly specific indicators of celiac disease(9,15), suggesting that this structure contains one or more target autoantigens that play a role in the pathogenesis of the disease(16,17). However, the identification of the endomysial autoantigen(s) has remained elusive. We identified tissue transglutaminase as the unknown endomysial autoantigen. Interestingly, gliadin is a preferred substrate for this enzyme, giving rise to novel antigenic epitopes.