Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea.
Association of HLA-DQ gene with bowel transit, barrier function, and inflammation in irritable bowel syndrome with diarrhea.
复制标题
HLA-DQ 基因与腹泻性肠易激综合征的肠道运输、屏障功能和炎症的关联。
DOI：
10.1152/ajpgi.00294.2012
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Zinsmeister,AlanR
中科院分区：
文献类型：
--
作者：
Vazquez-Roque,MariaI;Camilleri,Michael;Smyrk,Thomas;Murray,JosephA;O'Neill,Jessica;Carlson,Paula;Lamsam,Jesse;Eckert,Deborah;Janzow,Denise;Burton,Duane;Ryks,Michael;Rhoten,Deborah;Zinsmeister,AlanR
携带人类白细胞抗原（HLA）-DQ 2/8基因型的肠易激综合征（IBS）伴腹泻（IBS-D）患者从麸质戒断中获益。我们的目的是比较非乳糜泻IBS-D患者的胃肠屏障功能、粘膜炎症和转运，并评估与HLA-DQ 2/8状态的相关性。在45例未接受过麸质饮食的IBS-D患者中，我们通过累积尿乳果糖和甘露醇排泄量来测量小肠（SB）和结肠粘膜通透性（SB为0-2 h，结肠为8-24 h），十二指肠和直肠乙状结肠粘膜活检炎症（在45名患者中的28名中获得）、SB和直肠乙状结肠粘膜中的紧密连接（TJ）蛋白mRNA和蛋白表达以及通过经验证的结肠造影的胃肠和结肠转运。SB粘膜活检用苏木精-伊红染色以评估绒毛和上皮内淋巴细胞，免疫组织化学用于评估CD 3、CD 8、类胰蛋白酶和闭合小带1（ZO-1）;结肠活检上皮内淋巴细胞进行定量。使用Wilcoxon秩和检验评估HLA-DQ的关联性。相对于健康对照数据，我们观察到IBS-D患者SB渗透性显著增加（P< 0.001），结肠渗透性临界增加（P= 0.10），直肠乙状结肠粘膜TJ mRNA表达降低。在HLA-DQ 2/8阳性患者中，直肠乙状结肠粘膜中ZO-1蛋白表达较HLA-DQ 2/8阴性患者减少，结肠传输较HLA-DQ 2/8阴性患者慢。未发现与HLA基因型的其他相关性。IBS-D患者屏障功能异常（SB通透性增加和TJ蛋白mRNA表达降低），这可能部分与免疫基因型有关，因为HLA-DQ 2/8阳性患者直肠乙状结肠粘膜中ZO-1蛋白表达相对于HLA-DQ 2/8阴性患者减少。
Patients with irritable bowel syndrome (IBS) with diarrhea (IBS-D) carrying human leukocyte antigen (HLA)-DQ2/8 genotypes benefit from gluten withdrawal. Our objective was to compare gastrointestinal barrier function, mucosal inflammation, and transit in nonceliac IBS-D patients and assess association with HLA-DQ2/8 status. In 45 IBS-D patients who were naive to prior exclusion of dietary gluten, we measured small bowel (SB) and colonic mucosal permeability by cumulative urinary lactulose and mannitol excretion (0–2 h for SB and 8–24 h for colon), inflammation on duodenal and rectosigmoid mucosal biopsies (obtained in 28 of 45 patients), tight junction (TJ) protein mRNA and protein expression in SB and rectosigmoid mucosa, and gastrointestinal and colonic transit by validated scintigraphy. SB mucosal biopsies were stained with hematoxylin-eosin to assess villi and intraepithelial lymphocytes, and immunohistochemistry was used to assess CD3, CD8, tryptase, and zonula occludens 1 (ZO-1); colonic biopsy intraepithelial lymphocytes were quantitated. Associations of HLA-DQ were assessed using Wilcoxon's rank-sum test. Relative to healthy control data, we observed a significant increase in SB permeability (P< 0.001), a borderline increase in colonic permeability (P= 0.10), and a decrease in TJ mRNA expression in rectosigmoid mucosa in IBS-D. In HLA-DQ2/8-positive patients, ZO-1 protein expression in the rectosigmoid mucosa was reduced compared with that in HLA-DQ2/8-negative patients and colonic transit was slower than in HLA-DQ2/8-negative patients. No other associations with HLA genotype were identified. There is abnormal barrier function (increased SB permeability and reduced mRNA expression of TJ proteins) in IBS-D relative to health that may be, in part, related to immunogenotype, given reduced ZO-1 protein expression in rectosigmoid mucosa in HLA-DQ2/8-positive relative to HLA-DQ2/8-negative patients.
登录
查看更多内容
猪实验性急性肝衰竭中高氨血症、非氨依赖性昏迷
影响因子：
29.4
作者：
S. Schalm
通讯作者：
S. Schalm
影响因子：
3.5
作者：
Camilleri M;Iturrino J;Bharucha AE;Burton D;Shin A;Jeong ID;Zinsmeister AR
通讯作者：
Zinsmeister AR
影响因子：
12.6
作者：
Wahnschaffe, Ulrich;Schulzke, Joerg-Dieter;Ullrich, Reiner
通讯作者：
Ullrich, Reiner
无乳糜泻证据的麸质敏感性腹泻。
影响因子：
29.4
作者：
B. Cooper;G. Holmes;R. Ferguson;R. Thompson;R. Allan;W. Cooke
通讯作者：
W. Cooke
756 无麸质 (GFD) 和含麸质饮食 (GCD) 对腹泻性肠易激综合征 (IBS-D) 胃肠道和结肠运输、渗透性和小肠炎症的影响：一项随机研究
影响因子：
29.4
作者：
M. Vázquez;M. Camilleri;J. Murray;T. Smyrk;Jessica O’Neill;P. Carlson;J. Lamsam;D. Eckert;D. Burton;D. Janzow;A. Zinsmeister
通讯作者：
A. Zinsmeister