The role of the immune response against tissue transglutaminase in the pathogenesis of coeliac disease
The role of the immune response against tissue transglutaminase in the pathogenesis of coeliac disease
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DOI：
10.1016/s1568-9972(03)00054-5
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发表时间：
2004-02-01
影响因子：
13.6
通讯作者：
Schuppan, D
中科院分区：
文献类型：
--
作者：
Freitag, T;Schulze-Koops, H;Schuppan, D
对组织转氨酶（TGase 2）的自身免疫的发展是乳糜泻的显著特征，乳糜泻是一种在暴露于膳食麸质后在遗传易感个体中发展的肠病。伊加抗TGase 2自身抗体存在于至少98%的乳糜泻患者的含麸质饮食中，并为疾病的诊断提供了有价值的工具。在疾病发展过程中，通过TGase 2活性形成TGase 2-麦醇溶蛋白复合物似乎是B细胞表位从麦醇溶蛋白扩散到TGase 2的中心。然而，针对TGase 2的免疫应答在乳糜泻发病机制和肠道病变发展中的潜在作用仍不清楚。最近，已经描述了来自腹腔患者的抗TGase 2自身抗体在体外对TGase 2活性的抑制作用。在这里，我们报告了针对TGase 2的细胞和体液应答可以在TGase 2（-/-）和野生型小鼠中在C57 BL/6背景下通过s.c.用人重组或豚鼠TGase 2在完全弗氏佐剂中免疫。免疫的野生型小鼠，而非TGase 2（-/-）小鼠在泪腺中发生导管周淋巴细胞浸润。虽然没有发现肠道病变，但这一观察结果支持了这样的概念，即针对TGase 2的自身免疫的发展是一种可能最终导致器官损伤的病理事件。(C)2003 Elsevier Science B. V.保留所有权利。
The development of autoimmunity to tissue transglutaminase (TGase 2) is a striking feature of coeliac disease, an enteropathy that develops in genetically susceptible individuals upon exposure to dietary gluten. IgA anti-TGase 2 autoantibodies are present in at least 98% of coeliac patients on a gluten-containing diet and provide a valuable tool for the diagnosis of the disorder. During disease development, the formation of TGase 2-gliadin complexes through TGase 2 activity appears to be central for B-cell epitope spreading from gliadin to TGase 2. However, the potential role of an immune response against TGase 2 in the pathogenesis of coeliac disease and for the development of the intestinal lesion remains unclear. Recently, an inhibitory effect of anti-TGase 2 autoantibodies from coeliac patients on TGase 2 activity in vitro has been described. Here, we report that a cellular and humoral response against TGase 2 can be induced in TGase 2 (-/-) and wildtype mice on a C57BL/6 background by s.c. immunization with human recombinant or guinea pig TGase 2 in complete Freund's adjuvant. Immunized wildtype, but not TGase 2 (-/-) mice develop periductal lymphocytic infiltrates in lacrimal glands. Although no intestinal lesions were found, this observation lends support to the concept that the development of autoimmunity against TGase 2 is a pathological event that might ultimately lead to organ damage. (C) 2003 Elsevier Science B.V. All rights reserved.