Paediatric Research Center, University of Tampere and Tampere University Hospital, Tampere, Finland.
Autoimmun Rev. 2010 Sep;9(11):744-9. doi: 10.1016/j.autrev.2010.06.003. Epub 2010 Jun 12.
Celiac disease comprises intolerance against dietary gluten present in wheat, rye and barley, and it belongs to the most common food-related life-long disorders in Western countries. Nowadays celiac disease is conceived as an autoimmune-mediated systemic disorder commonly presenting as enteropathy in genetically susceptible individuals. The most obvious feature distinguishing celiac disease from other small-intestinal enteropathies is the presence of autoantibodies against transglutaminase 2 (TG2) during a gluten-containing diet. The gluten-derived gliadin peptides and the self, TG2, have established and well-accepted role in celiac disease pathogenesis. TG2 is known to deamidate, and crosslink gluten-derived gliadin peptides to itself, thereby favoring disease progression. The celiac disease-specific TG2-targeted autoantibodies are deposited in the small-bowel mucosa as well as in other tissues, and interestingly, extraintestinal manifestations of the disease involving these particular tissues have been reported. As the TG2-targeted autoantibodies have experimentally been shown to modulate the function of different cell types in vitro similarly to what has been reported to occur in untreated celiac disease, they could constitute an important contribution to disease progression. In this review we discuss the role of TG2, the autoantigen and the autoantibodies targeted against it in the pathogenesis of celiac disease.
乳糜泻是一种对小麦、黑麦和大麦中存在的膳食麸质不耐受的疾病，它属于西方国家最常见的与食物相关的终身疾病之一。如今，乳糜泻被认为是一种自身免疫介导的系统性疾病，通常在遗传易感个体中表现为肠病。将乳糜泻与其他小肠肠病区分开来的最明显特征是在含有麸质的饮食中存在针对转谷氨酰胺酶 2（TG2）的自身抗体。源自麸质的麦胶蛋白肽和自身 TG2 在乳糜泻发病机制中具有既定且公认的作用。已知 TG2 可使源自麸质的麦胶蛋白肽脱酰胺并与自身交联，从而促进疾病进展。乳糜泻特异性靶向 TG2 的自身抗体沉积在小肠黏膜以及其他组织中，有趣的是，已经报道了涉及这些特定组织的疾病的肠外表现。由于实验已经表明 TG2 靶向自身抗体可以调节体外不同细胞类型的功能，类似于在未经治疗的乳糜泻中发生的情况，因此它们可能是疾病进展的重要贡献因素。在这篇综述中，我们讨论了 TG2、自身抗原以及针对其的自身抗体在乳糜泻发病机制中的作用。
