Multigene Analysis Unveils Distinctive Expression Profiles of Helper T-cell-related Genes in the Intestinal Mucosa that Discriminate Between Ulcerative Colitis and Crohn's Disease
Multigene Analysis Unveils Distinctive Expression Profiles of Helper T-cell-related Genes in the Intestinal Mucosa that Discriminate Between Ulcerative Colitis and Crohn's Disease
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DOI：
10.1097/mib.0000000000000028
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发表时间：
2014-06-01
影响因子：
4.9
通讯作者：
Takayanagi, Ryoichi
中科院分区：
文献类型：
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作者：
Iboshi, Yoichiro;Nakamura, Kazuhiko;Takayanagi, Ryoichi
背景：尽管辅助性 T (Th) 和调节性 T (Treg) 细胞相关免疫分子参与炎症性肠病 (IBD) 的发病机制已被广泛接受，但这些分子在溃疡性结肠炎 (UC) 和克罗恩病 (CD) 之间的粘膜表达谱尚未明确。方法：通过定量 PCR 检测与 Th1、Th2、Th17 和 Treg 相关的 17 种细胞因子和转录因子的粘膜表达。发炎结肠或回肠（40 个来自 UC [UCI]，20 个来自 CD [CDI]）和非发炎结肠或回肠（分别为 47、22 和 25 个来自 UC、CD 和对照）的内镜活检。通过线性判别分析和无监督主成分分析来评估这些标记物区分两种疾病的辨别力。结果：通过单变量分析，与非炎症区域相比，许多目标在炎症区域显着增加。然而，UCI 和 CDI 之间的标志物表达几乎相当，其中以 UCI 为主的白细胞介素 (IL) 21 和 IL-13 差异最大，受试者工作特征曲线下面积 (AUC) 值分别为 0.704 和 0.664。相反，2 至 7 个标记物的组合改善了 UCI 与 CDI 的区分度，AUC 为 0.875 至 0.975。其中，5 个标记集（干扰素-gamma、IL-12 p35、T-bet、GATA3 和 IL-21）的 AUC 为 0.949，错误分类率为 8.3%。主成分分析也显着区分了 UCI 和 CDI。结论：使用 Th 细胞相关标记物的组合可以高精度地区分 UC 和 CD 的发炎粘膜。多基因分析可能反映潜在的发病机制，预计将有助于诊断、监测和进一步确定炎症性肠病的独特特征。
Background: Although the involvement of helper T (Th) and regulatory T (Treg) cell-related immune molecules in pathogenesis of inflammatory bowel disease (IBD) is widely accepted, no discriminatory mucosal expression profiles of these molecules between ulcerative colitis (UC) and Crohn's disease (CD) have been clarified.Methods: Mucosal expression of 17 cytokines and transcription factors related to Th1, Th2, Th17, and Treg were measured by quantitative PCR in endoscopic biopsies from inflamed (40 from UC [UCI] and 20 from CD [CDI]) and noninflamed (47, 22, and 25 from UC, CD, and controls, respectively) colon or ileum. The discriminatory power of these markers to differentiate between the 2 diseases was evaluated by linear discriminant analysis and, unsupervised, principal component analysis.Results: By univariate analysis, many targets were markedly increased in inflamed versus noninflamed areas. However, marker expression was almost comparable between UCI and CDI, with the largest difference in UCI-predominant interleukin (IL) 21 and IL-13 with area under the receiver operating characteristic curve (AUC) values of 0.704 and 0.664, respectively. In contrast, combinations of 2 to 7 markers improved UCI versus CDI discrimination with AUC 0.875 to 0.975. Among these, a 5-maker set (interferon-gamma, IL-12 p35, T-bet, GATA3, and IL-21) demonstrated an AUC of 0.949 and a misclassification rate of 8.3%. Principal component analysis also markedly separated UCI and CDI.Conclusions: Inflamed mucosae from UC and CD could be discriminated with high accuracy using combinations of Th cell-related markers. Multigene analysis, possibly reflecting the underlying pathogenesis, is expected to be useful for diagnosis, monitoring and further defining distinctive characteristics in inflammatory bowel disease.