Genentech Research and Early Development, South San Francisco, California, USA.
Newcastle University, Newcastle upon Tyne, UK.
J Crohns Colitis. 2018 Nov 9;12(10):1191-1199. doi: 10.1093/ecco-jcc/jjy084.
Recent findings suggest that αE expression is enriched on effector T cells and that intestinal αE+ T cells have increased expression of inflammatory cytokines. αE integrin expression is a potential predictive biomarker for response to etrolizumab, a monoclonal antibody against β7 integrin that targets both α4β7 and αEβ7. We evaluated the prevalence and localization of αE+ cells as well as total αE gene expression in healthy and inflammatory bowel disease patients.
αE+ cells were identified in ileal and colonic biopsies by immunohistochemistry and counted using an automated algorithm. Gene expression was assessed by quantitative reverse-transcriptase polymerase chain reaction.
In both healthy and inflammatory bowel disease patients, significantly more αE+ cells were present in the epithelium and lamina propria of ileal compared with colonic biopsies. αE gene expression levels were also significantly higher in ileal compared with colonic biopsies. Paired biopsies from the same patient showed moderate correlation of αE expression between the ileum and colon. Inflammation did not affect αE expression, and neither endoscopy nor histology scores correlated with αE gene expression. αE expression was not different between patients based on concomitant medication use except 5-aminosalicylic acid.
αE+ cells, which have been shown to have inflammatory potential, are increased in the ileum in comparison with the colon in both Crohn's disease and ulcerative colitis, as well as in healthy subjects. In inflammatory bowel disease patients, αE levels are stable, regardless of inflammatory status or most concomitant medications, which could support its use as a biomarker for etrolizumab.
最近的研究结果表明，αE 表达在效应 T 细胞中丰富，并且肠道 αE+T 细胞中炎症细胞因子的表达增加。αE 整合素的表达是对 etrolizumab（一种针对β7 整合素的单克隆抗体，靶向α4β7 和 αEβ7）反应的潜在预测生物标志物。我们评估了健康人和炎症性肠病患者中 αE+细胞的流行率和定位以及总 αE 基因表达。
通过免疫组织化学鉴定回肠和结肠活检中的 αE+细胞，并使用自动算法进行计数。通过定量逆转录聚合酶链反应评估基因表达。
在健康人和炎症性肠病患者中，与结肠活检相比，回肠的上皮和固有层中存在更多的 αE+细胞。与结肠活检相比，αE 基因表达水平也显著升高。来自同一患者的配对活检显示，回肠和结肠之间的 αE 表达具有中等相关性。炎症并未影响 αE 表达，内镜检查和组织学评分均与 αE 基因表达无关。除了 5-氨基水杨酸外，基于同时使用的药物，患者之间的 αE 表达没有差异。
与结肠相比，克罗恩病和溃疡性结肠炎以及健康受试者的回肠中 αE+细胞增加，这些细胞具有潜在的炎症作用。在炎症性肠病患者中，αE 水平稳定，无论炎症状态或大多数伴随药物如何，这可能支持将其用作 etrolizumab 的生物标志物。
