Günaltay Sezin, Repsilber Dirk, Helenius Gisela, Nyhlin Nils, Bohr Johan, Hultgren Olof, Hultgren Hörnquist Elisabeth
*Nutrition-Gut-Brain Interactions Research Centre, Faculty of Health and Medicine, School of Medical Sciences, Örebro University, Örebro, Sweden; †Department of Pathology, Örebro University Hospital, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; ‡Department of Medicine, Division of Gastroenterology, Örebro University Hospital, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; and §Department of Microbiology and Immunology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
Inflamm Bowel Dis. 2017 Jun;23(6):932-945. doi: 10.1097/MIB.0000000000001127.
Microscopic colitis (MC), comprising collagenous colitis (CC) and lymphocytic colitis (LC), is a type of variation of inflammatory bowel diseases. Local T-cell infiltration in the mucosa plays a major role in MC immunopathology.
To understand diversity and clonality of infiltrating T cells, we analyzed the T-cell receptor beta (TCRβ) chains in colonic biopsies of MC, ulcerative colitis (UC), and their remission counterparts (CC/LC-HR [histological remission] or UC-R [remission]) compared with patients with noninflamed colons using next-generation sequencing.
Compared with controls and patients with CC, patients with LC had significantly lower diversity with significantly lower evenness and richness in TCRVβ-Jβ gene segments. Similarly, patients with LC-HR had lower diversity because of significantly lower TCRVβ-Jβ clone richness. Patients with UC and UC-R showed significantly higher diversity and richness. Univariate and multivariate analyses were performed to identify TCRVβ-Jβ gene segments differentiating disease types from controls or their remission counterparts. Patients with LC were discriminated from controls by 12 clones and from patients with CC by 8 clones. Neither univariate nor multivariate analyses showed significance for patients with CC or CC-HR compared with controls. Patients with UC and UC-R had 16 and 14 discriminating clones, respectively, compared with controls.
Altogether, patients with MC and UC showed an oligoclonal TCRβ distribution. TCRVβ-Jβ clone types and their diversity were distinctive between patients with CC and LC, as well as for patients with UC, suggesting different pathophysiological mechanisms according to disease type and stage. This study suggests that CC and LC are different entities because of differences in immunoregulatory responses, as mirrored by their T-cell repertoire.
显微镜下结肠炎（MC）包括胶原性结肠炎（CC）和淋巴细胞性结肠炎（LC），是炎症性肠病的一种变异类型。黏膜中的局部T细胞浸润在MC免疫病理学中起主要作用。
为了解浸润性T细胞的多样性和克隆性，我们使用下一代测序分析了MC、溃疡性结肠炎（UC）及其缓解期对应患者（CC/LC-HR[组织学缓解]或UC-R[缓解]）的结肠活检组织中的T细胞受体β（TCRβ）链，并与非炎症性结肠患者进行了比较。
与对照组和CC患者相比，LC患者的多样性显著降低，TCRVβ-Jβ基因片段的均匀度和丰富度也显著降低。同样，LC-HR患者的多样性较低，因为TCRVβ-Jβ克隆丰富度显著降低。UC和UC-R患者的多样性和丰富度显著更高。进行单变量和多变量分析以确定区分疾病类型与对照组或其缓解期对应患者的TCRVβ-Jβ基因片段。LC患者与对照组通过12个克隆区分，与CC患者通过8个克隆区分。与对照组相比，CC或CC-HR患者的单变量和多变量分析均无显著性差异。与对照组相比，UC和UC-R患者分别有16个和14个区分克隆。
总体而言，MC和UC患者表现出寡克隆TCRβ分布。CC和LC患者之间以及UC患者的TCRVβ-Jβ克隆类型及其多样性是不同的，这表明根据疾病类型和阶段存在不同的病理生理机制。这项研究表明，CC和LC是不同的实体，因为它们的免疫调节反应不同，这反映在它们的T细胞库中。
