Koning Frits, Gilissen Luud, Wijmenga Cisca
Department of Immunohematology and Blood Transfusion, Leiden University Medical Centre, E3-Q, P.O. Box 9600, 2300 RC, Leiden, The Netherlands.
Springer Semin Immunopathol. 2005 Sep;27(2):217-32. doi: 10.1007/s00281-005-0203-9. Epub 2005 Aug 10.
Celiac disease (CD) is a small intestinal disorder caused by adaptive and innate immune responses triggered by the gluten proteins present in wheat. In the intestine, gluten is partially degraded and modified, which results in gluten peptides that bind with high affinity to HLA-DQ2 or HLA-DQ8 and trigger an inflammatory T cell response. Simultaneously, gluten exposure leads to increased production of IL15, which induces the expression of NKG2D on intraepithelial lymphocytes and its ligand MICA on epithelial cells, leading to epithelial cell destruction. The gluten-specific T cell response results in the production of antibodies against tissue transglutaminase and these are specific indicators of disease. CD is one of the most common inherited diseases, the HLA-DQ locus being the major contributing genetic factor. However, as the inheritance does not follow a Mendelian segregation pattern, multiple other genes, each with relative weak effect, contribute to disease development. An important role for environmental factors, however, can not be ignored as the concordance rate in monozygous twins is considerably less than 100%. The identification of these environmental factors and susceptibility genes may allow a better understanding of disease etiology and provide diagnostic and prognostic markers. The current treatment for CD consists of a life-long gluten-free diet. Although long thought to be impossible, recent results suggest that the development of nontoxic wheat varieties may be feasible, which would aid disease prevention and provide an alternative food source for patients.
乳糜泻（CD）是一种小肠疾病，由小麦中存在的麸质蛋白引发的适应性和先天性免疫反应所致。在肠道中，麸质被部分降解和修饰，从而产生与HLA-DQ2或HLA-DQ8高亲和力结合并触发炎症性T细胞反应的麸质肽。同时，接触麸质会导致IL15产生增加，IL15会诱导上皮内淋巴细胞上NKG2D及其配体MICA在上皮细胞上的表达，从而导致上皮细胞破坏。麸质特异性T细胞反应会产生针对组织转谷氨酰胺酶的抗体，这些抗体是疾病的特异性指标。CD是最常见的遗传性疾病之一，HLA-DQ基因座是主要的致病遗传因素。然而，由于遗传不遵循孟德尔分离模式，多个其他基因（每个基因的作用相对较弱）也参与疾病的发展。然而，环境因素的重要作用不容忽视，因为同卵双胞胎中的一致率远低于100%。识别这些环境因素和易感基因可能有助于更好地理解疾病病因，并提供诊断和预后标志物。目前CD的治疗方法是终生无麸质饮食。尽管长期以来认为这是不可能的，但最近的结果表明，培育无毒小麦品种可能是可行的，这将有助于疾病预防，并为患者提供替代食物来源。
