University of Rome "La Sapienza", Via di Novella, 11, 00199, Rome, Italy.
J Crohns Colitis. 2008 Dec;2(4):352-6. doi: 10.1016/j.crohns.2008.06.001. Epub 2008 Aug 8.
Crohn's disease can affect any part of the gastrointestinal tract, but terminal ileum is the most frequent localization. The reason why Crohn's disease is primarily located in the distal part of the ileum remains unexplained. In this article it has been attempted to provide a compelling explanation why Crohn's disease usually occurs in terminal ileum. Recent data indicate that some individuals are genetically predisposed to develop ileal Crohn's disease. Two genetic alterations, the polymorphism of Caspase Associated Recruitment Domain (CARD15) and Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 (CEACM6), favour the colonization of terminal ileum by entero adherent-invasive Escherichia coli (AIEC). The adhesion of these bacteria to epithelial intestinal cells depends on Carcinoembryonic Antigen-related Cell Adhesion Molecule 6 expression in ileal epithelial cells and on the reduced ileal defensins expressed in a CARD15 dependent manner. Genetic defects in Authophagy-related 16-like gene (ATG16L1) and Immunity-related Guanosine Triphospatase (IRGM) recently found in ileal CD patients lead to a reduction of bacterial killing by macrophages and consequent continuous immunological upstimulation, cytokine secretion, chronic inflammation of the ileum and tissue injury. On the basis of all these data Crohn's disease of the ileum seems to be a subset of the disease mainly genetically determined.
克罗恩病可影响胃肠道的任何部位，但回肠末端是最常见的发病部位。然而，为什么克罗恩病主要位于回肠的远段，其原因仍不清楚。本文试图提供一个令人信服的解释，说明为什么克罗恩病通常发生在回肠末端。最近的数据表明，某些个体易患回肠克罗恩病，这与两种遗传改变有关，即半胱氨酸天冬氨酸蛋白酶相关募集域（CARD15）和癌胚抗原相关细胞黏附分子 6（CEACM6）的多态性，有利于肠侵袭性大肠杆菌（AIEC）定植于回肠末端。这些细菌与肠上皮细胞的黏附取决于回肠上皮细胞中癌胚抗原相关细胞黏附分子 6的表达，以及依赖 CARD15 表达的回肠防御素减少。在回肠 CD 患者中最近发现的自噬相关 16 样基因（ATG16L1）和免疫相关鸟嘌呤三磷酸酶（IRGM）的遗传缺陷导致巨噬细胞对细菌的杀伤减少，继而导致持续的免疫刺激、细胞因子分泌、回肠慢性炎症和组织损伤。基于所有这些数据，回肠克罗恩病似乎是一种主要由遗传决定的疾病亚类。
