Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn's disease
Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn's disease
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DOI：
10.1007/s00535-011-0425-7
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发表时间：
2011-09-01
影响因子：
6.3
通讯作者：
Hibi, Toshifumi
中科院分区：
文献类型：
--
作者：
Miyoshi, Jun;Yajima, Tomoharu;Hibi, Toshifumi
背景宿主-肠道微生物相互作用在炎症性肠病（IBD）的发病机制中起重要作用。肠上皮细胞的表面分子作为细菌粘附的受体并调节肠道细菌。一些已知的受体是粘膜血型抗原，其由岩藻糖基转移酶2（FUT 2）基因调节，并且在胃肠道中表达这些抗原的个体被称为分泌者。最近的研究表明，FUT 2基因与克罗恩病（CD）在西方populations.Methods澄清粘膜血型抗原在IBD的贡献，我们确定了五个以前报道的单核苷酸多态性的FUT 2基因在日本患者的发病率。我们还采用免疫组化方法研究IBD患者和动物模型粘膜标本中的抗原表达。结果基因分析显示，所有结肠CD患者均为分泌型，而对照组、回结肠CD组、回肠CD组和溃疡性结肠炎组的分泌型发生率分别为80%、80%、67%和80%（P = 0.036）。血型抗原的异常表达仅见于结肠CD。IL-10（-/-）小鼠结肠血型抗原表达增强，且这些抗原的表达早于IL-10（-/-）小鼠结肠炎的发生。结论FUT 2分泌状态与结肠型CD相关。这一发现，结合免疫组化数据，表明血型抗原在结肠的异常表达可能是一个独特的和必要的因素，结肠CD。
Background Host-intestinal microbial interaction plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). The surface molecules of the intestinal epithelium act as receptors for bacterial adhesion and regulate the intestinal bacteria. Some known receptors are the mucosal blood type antigens, which are regulated by the fucosyltransferase2 (FUT2) gene, and individuals who express these antigens in the gastrointestinal tract are called secretors. Recent research has revealed that the FUT2 gene is associated with Crohn's disease (CD) in western populations.Methods To clarify the contribution of mucosal blood type antigens in IBD, we determined the incidence of five previously reported single-nucleotide polymorphisms of the FUT2 gene in Japanese patients. We also used immunohistochemistry to investigate the antigen expression in mucosal specimens from IBD patients and animal models.Results Genetic analysis revealed that all of the patients with colonic CD were secretors, whereas the incidence of secretors was 80, 80, 67, and 80%, respectively, for the control, ileocolonic CD, ileal CD, and ulcerative colitis groups (P = 0.036). Abnormal expression of blood type antigens was observed only in colonic CD. Interleukin-10(-/-) mice, but not dextran sulfate sodium colitis mice, had enhanced colonic expression of blood type antigens, and the expression of these antigens preceded the development of colitis in the interleukin-10(-/-) mice.Conclusions FUT2 secretor status was associated with colonic-type CD. This finding, taken together with the immunohistochemistry data, suggests that the abnormal expression of blood type antigens in the colon may be a unique and essential factor for colonic CD.