Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity.
Divergence of gut permeability and mucosal immune gene expression in two gluten-associated conditions: celiac disease and gluten sensitivity.
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DOI：
10.1186/1741-7015-9-23
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发表时间：
2011-03-09
期刊：
影响因子：
9.3
通讯作者：
Fasano A
中科院分区：
文献类型：
--
作者：
Sapone A;Lammers KM;Casolaro V;Cammarota M;Giuliano MT;De Rosa M;Stefanile R;Mazzarella G;Tolone C;Russo MI;Esposito P;Ferraraccio F;Cartenì M;Riegler G;de Magistris L;Fasano A
乳糜泻（CD）是一种由麸质摄入引发的自身免疫性肠病。麸质敏感个体（GS）不能耐受麸质，可能会出现与CD相似的胃肠道症状，但总体临床表现通常不太严重，并且不伴有组织转氨酶自身抗体或自身免疫性合并症。通过研究和比较与肠屏障功能相关的基因的粘膜表达，以及与GS相比CD中的先天性和获得性免疫，我们试图更好地了解这两种谷蛋白相关疾病之间的相似性和差异。CD、GS和健康的、谷蛋白耐受的个体入组本研究。使用乳果糖和甘露醇探针评价肠通透性，并收集粘膜活检标本以研究涉及屏障功能和免疫的基因表达。与CD不同，GS与肠通透性增加无关。事实上，与对照组相比，这在GS中显著降低（P = 0.0308），其次是紧密连接蛋白（CLDN）4的表达显著增加（P = 0.0286）。与对照组相比，获得性免疫标志物白细胞介素（IL）-6（P = 0.0124）和IL-21（P = 0.0572）在CD中表达水平较高，但在GS中无表达，而先天免疫标志物Toll样受体（TLR）2在GS中表达增加，但在CD中无表达（P = 0.0295）。最后，相对于对照组（P = 0.0325）和CD患者（P = 0.0293），GS中T调节细胞标志物FOXP 3的表达显著降低。这项研究表明，这两个面筋相关的疾病，CD和GS，是不同的临床实体，它有助于表征GS作为一个条件与普遍的面筋诱导的先天性激活，而不是适应性，免疫反应在没有可检测到的粘膜屏障功能的变化。
Celiac disease (CD) is an autoimmune enteropathy triggered by the ingestion of gluten. Gluten-sensitive individuals (GS) cannot tolerate gluten and may develop gastrointestinal symptoms similar to those in CD, but the overall clinical picture is generally less severe and is not accompanied by the concurrence of tissue transglutaminase autoantibodies or autoimmune comorbidities. By studying and comparing mucosal expression of genes associated with intestinal barrier function, as well as innate and adaptive immunity in CD compared with GS, we sought to better understand the similarities and differences between these two gluten-associated disorders. CD, GS and healthy, gluten-tolerant individuals were enrolled in this study. Intestinal permeability was evaluated using a lactulose and mannitol probe, and mucosal biopsy specimens were collected to study the expression of genes involved in barrier function and immunity. Unlike CD, GS is not associated with increased intestinal permeability. In fact, this was significantly reduced in GS compared with controls (P = 0.0308), paralleled by significantly increased expression of claudin (CLDN) 4 (P = 0.0286). Relative to controls, adaptive immunity markers interleukin (IL)-6 (P = 0.0124) and IL-21 (P = 0.0572) were expressed at higher levels in CD but not in GS, while expression of the innate immunity marker Toll-like receptor (TLR) 2 was increased in GS but not in CD (P = 0.0295). Finally, expression of the T-regulatory cell marker FOXP3 was significantly reduced in GS relative to controls (P = 0.0325) and CD patients (P = 0.0293). This study shows that the two gluten-associated disorders, CD and GS, are different clinical entities, and it contributes to the characterization of GS as a condition associated with prevalent gluten-induced activation of innate, rather than adaptive, immune responses in the absence of detectable changes in mucosal barrier function.
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影响因子：
6.6
作者：
Cascella, Nicola G.;Kryszak, Debra;Eaton, William W.
通讯作者：
Eaton, William W.
影响因子：
3.8
作者：
Hewitt, Kyle J.;Agarwal, Rachana;Morin, Patrice J.
通讯作者：
Morin, Patrice J.
DOI：
10.1097/mpg.0b013e3181dcc4a5
发表时间：
2010-10-01
影响因子：
2.9
作者：
de Magistris, Laura;Familiari, Valeria;Bravaccio, Carmela
通讯作者：
Bravaccio, Carmela
DOI：
10.1083/jcb.141.7.1539
发表时间：
1998-06-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Furuse M;Fujita K;Hiiragi T;Fujimoto K;Tsukita S
通讯作者：
Tsukita S
影响因子：
48
作者：
Hadjivassiliou, Marios;Sanders, David S.;Aeschlimann, Daniel
通讯作者：
Aeschlimann, Daniel