In Well‐Treated Celiac Patients Low‐Level Mucosal Inflammation Predicts Response to 14‐day Gluten Challenge,Advanced Science

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In Well‐Treated Celiac Patients Low‐Level Mucosal Inflammation Predicts Response to 14‐day Gluten Challenge
Advanced Science ( IF 14.3 ) Pub Date : 2021-01-04 , DOI: 10.1002/advs.202003526
Jorunn Stamnaes _{1,

2} , Daniel Stray _{1,

2} , Maria Stensland ₂ , Vikas K Sarna ₃ , Tuula A Nyman ₂ , Knut E A Lundin _{1,

4} , Ludvig M Sollid _{1,

2}

Affiliation

In celiac disease (CeD), gluten activates adaptive immune cells that cause damage to the small intestinal mucosa. Histological evaluation of intestinal biopsies allows for grading of disease severity. CeD can effectively be treated with a life‐long gluten‐free diet. Gluten challenge of treated CeD patients is used to confirm diagnosis and to test drug efficacy in clinical trials, but patients respond with different magnitudes to the same gluten challenge. In this study of 19 well‐treated CeD patients, proteome analysis of total tissue or isolated epithelial cell compartment from formalin‐fixed paraffin embedded biopsies collected before and after 14‐day gluten challenge demonstrates that patients with strong mucosal response to challenge have signs of ongoing tissue inflammation already before challenge. This low‐level tissue inflammation at baseline is paralleled by increased gluten specific CD4+ T‐cell frequencies in the gut and presence of a low‐level blood inflammatory profile. Thus, apparently well‐treated CeD is frequently not entirely quiescent, with presence of low‐grade inflammation and antigluten immunity in the gut mucosa. Histology assessment alone appears insufficient to judge full recovery and gut mucosal healing of CeD patients. The findings raise a concern whether a seemingly proper gluten‐free diet is able to curb gut inflammation in all CeD patients.

中文翻译：

在治疗良好的乳糜泻患者中，低水平的粘膜炎症预示着对 14 天麸质挑战的反应

在乳糜泻 (CeD) 中，麸质会激活适应性免疫细胞，从而对小肠粘膜造成损害。肠道活检的组织学评估可以对疾病严重程度进行分级。终身无麸质饮食可以有效治疗 CeD。接受治疗的 CeD 患者的麸质挑战用于确认诊断并在临床试验中测试药物疗效，但患者对相同的麸质挑战的反应程度不同。在这项针对 19 名接受良好治疗的 CeD 患者的研究中，对 14 天麸质挑战前后收集的福尔马林固定石蜡包埋的活检组织或分离的上皮细胞区室进行蛋白质组分析，结果表明，对挑战有强烈粘膜反应的患者有持续的迹象。在挑战之前组织就已经发炎了。这种基线时的低水平组织炎症与肠道中麸质特异性 CD4+ T 细胞频率的增加以及低水平血液炎症特征的存在是平行的。因此，显然经过良好治疗的 CeD 通常并不完全静止，肠道粘膜中存在低度炎症和抗麸质免疫。单独的组织学评估似乎不足以判断 CeD 患者的完全恢复和肠粘膜愈合。这些发现引起了人们的关注，即看似适当的无麸质饮食是否能够抑制所有 CeD 患者的肠道炎症。

更新日期：2021-02-17

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