固有层辅助性T细胞亚群特征可区分溃疡性结肠炎和克罗恩病。

Profiles of Lamina Propria T Helper Cell Subsets Discriminate Between Ulcerative Colitis and Crohn's Disease.

作者信息

Li Ji, Ueno Aito, Fort Gasia Miriam, Luider Joanne, Wang Tie, Hirota Christina, Jijon Humberto B, Deane Mailin, Tom Michael, Chan Ronald, Barkema Herman W, Beck Paul L, Kaplan Gilaad G, Panaccione Remo, Qian Jiaming, Iacucci Marietta, Gui Xinyang, Ghosh Subrata

机构信息

*Department of Medicine/Gastroenterology, University of Calgary, Calgary, Alberta, Canada;†Department of Gastroenterology, Peking Union Medical College Hospital, Beijing, China;‡Calgary Laboratory Services, Calgary, Alberta, Canada;§Department of Pathology and Laboratory Medicine, University of Calgary, Calgary, Alberta, Canada; and‖Department of Production Animal Health, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada.

出版信息

Inflamm Bowel Dis. 2016 Aug;22(8):1779-92. doi: 10.1097/MIB.0000000000000811.

DOI:10.1097/MIB.0000000000000811

PMID:27243594

Abstract

BACKGROUND

Distinction between 2 forms of inflammatory bowel disease (IBD), ulcerative colitis (UC) and Crohn's disease (CD), can be challenging. Aberrant mucosal immunity suggests that CD is a T helper type 1 cell (Th1)-driven disease, whereas UC as Th2-driven response. However, whether this paradigm truly distinguishes CD from UC is controversial. We aimed to clarify the discriminating potential of lamina propria Th subsets in patients with IBD.

METHODS

Biopsies from 79 patients with IBD and 20 healthy controls were collected for Th subsets analysis (Th1:interferon γ [IFN-γ], T-bet; Th2:interleukin 13 [IL-13], Gata3; Th17:IL-17, RORγt; Treg:FoxP3). The receiver-operating characteristic curves were constructed to assess the discriminating ability by calculating the area under the receiver-operating characteristic curve. The equation with the highest area under the receiver-operating characteristic curve was applied to newly diagnosed patients to evaluate discriminating ability.

RESULTS

Patients with CD showed increased IFN-γ or T-bet cells and decreased IL-13 or Gata3 cells compared with UC. A discriminant equation composed of 4 markers (IFN-γ, T-bet, IL-13, and Gata3) yielded the highest area under the receiver-operating characteristic curve. In 36 established CD or UC, the sensitivity, specificity, positive and negative predictive probabilities were 92.6%, 55.6%, 86.2%, and 71.4% and in 14 newly diagnosed patients were 100.0%, 42.9%, 63.6%, and 100.0%. Furthermore, Gata3 cells were increased in tumor necrosis factor inhibitor therapy nonresponders compared with responders in CD. IFN-γ cells were directly and inversely proportional to disease activity in patients with CD and UC, respectively.

CONCLUSIONS

The Th1/Th2 paradigm can distinguish CD from UC and may be further associated with response to tumor necrosis factor inhibitor in CD and disease activity in patients with IBD.

摘要

背景

区分两种炎症性肠病（IBD），即溃疡性结肠炎（UC）和克罗恩病（CD）具有挑战性。异常的黏膜免疫表明，CD是一种由1型辅助性T细胞（Th1）驱动的疾病，而UC是由Th2驱动的反应。然而，这种模式是否真的能将CD与UC区分开来存在争议。我们旨在阐明IBD患者固有层Th亚群的鉴别潜力。

方法

收集79例IBD患者和20例健康对照的活检组织进行Th亚群分析（Th1：干扰素γ[IFN-γ]、T-bet；Th2：白细胞介素13[IL-13]、Gata3；Th17：IL-17、RORγt；调节性T细胞：FoxP3）。构建受试者工作特征曲线，通过计算受试者工作特征曲线下面积来评估鉴别能力。将受试者工作特征曲线下面积最大的方程应用于新诊断患者以评估鉴别能力。

结果

与UC相比，CD患者的IFN-γ或T-bet细胞增加，IL-13或Gata3细胞减少。由4种标志物（IFN-γ、T-bet、IL-13和Gata3）组成的判别方程产生了最高的受试者工作特征曲线下面积。在36例确诊的CD或UC患者中，敏感性、特异性、阳性和阴性预测概率分别为92.6%、55.6%、86.2%和71.4%，在14例新诊断患者中分别为100.0%、42.9%、63.6%和100.0%。此外，与CD中肿瘤坏死因子抑制剂治疗有反应者相比，无反应者的Gata3细胞增加。IFN-γ细胞分别与CD和UC患者的疾病活动呈直接和反比关系。