Monsuur Alienke J, Wijmenga Cisca
Complex Genetics Section, Department of Biomedical Genetics, UMC Utrecht, The Netherlands.
Ann Med. 2006;38(8):578-91. doi: 10.1080/07853890600989054.
Celiac disease (CD) is characterized by a chronic immune reaction in the small intestine to the gluten proteins that are present in a (Western) daily diet. Besides the well known involvement of the HLA class II histocompatibility antigen (HLA)-DQ2.5 and -DQ8 heterodimers (encoded by particular combinations of the HLA-DQA1 and -DQB1 gene) in CD and the minor contribution of the CTLA-4 gene, recently the myosin IXB (MYO9B) gene has also been found to be genetically associated. This review covers the general aspects of CD as well as current insight into important molecular aspects. We evaluate the role of susceptibility genes in CD by following gluten along its path from ingestion to uptake in the body, which leads us through the three aspects of CD's pathology. The first is the presence of gluten in the lumen of the intestine, where it is broken down by several enzymes. The second is the intestinal barrier through which gluten peptides pass. The third is the reaction of the immune system in response to gluten peptides, in which both the innate and the adaptive immune systems play a role. Our main conclusion, based on the current genetic and functional studies, is that we should look for causal genes in the barrier function as well as in the immune systems.
乳糜泻（CD）的特征是小肠对日常（西方）饮食中存在的麸质蛋白产生慢性免疫反应。除了众所周知的人类白细胞抗原（HLA）II类组织相容性抗原HLA - DQ2.5和 - DQ8异二聚体（由HLA - DQA1和 - DQB1基因的特定组合编码）在乳糜泻中的作用以及细胞毒性T淋巴细胞相关抗原4（CTLA - 4）基因的微小贡献外，最近还发现肌球蛋白IXB（MYO9B）基因与乳糜泻存在遗传关联。本综述涵盖了乳糜泻的一般方面以及对重要分子方面的当前见解。我们通过追踪麸质从摄入到在体内吸收的过程来评估易感基因在乳糜泻中的作用，这使我们了解乳糜泻病理的三个方面。第一个方面是肠道腔内存在麸质，它会被几种酶分解。第二个方面是麸质肽穿过的肠道屏障。第三个方面是免疫系统对麸质肽的反应，其中固有免疫系统和适应性免疫系统都发挥作用。基于当前的遗传和功能研究，我们的主要结论是，我们应该在屏障功能以及免疫系统中寻找致病基因。
