Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Kussmaul Campus for Medical Research & Translational Research Center, Ulmenweg 18, 91054, Erlangen, Germany.
BMC Gastroenterol. 2020 Apr 15;20(1):103. doi: 10.1186/s12876-020-01253-8.
While the number of therapeutic options for treating inflammatory bowel diseases (IBD) is increasing, evidence for rational treatment decisions is scarce in many cases. In particular, appropriate biomarkers to predict the response to the anti-α4β7 integrin antibody vedolizumab are currently lacking.
We performed a cohort study with 21 patients suffering from ulcerative colitis (UC), in which first-time treatment with vedolizumab was initiated. CD4 T cells were isolated from the peripheral blood and dynamic adhesion to recombinant mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in vitro as well as the effect of vedolizumab on such adhesion in vitro was determined. The expression of α4β1 integrin on peripheral blood CD4 T cells was quantified by flow cytometry. Electronic patient records were reviewed to determine clinical response to vedolizumab.
Dynamic adhesion of peripheral blood CD4 T cells to MAdCAM-1 and the reduction of adhesion following vedolizumab treatment in vitro were higher and the change in α4β1 expression on CD4 T cells was different in vedolizumab responders and non-responders. Responders could be identified with high specificity and positive-predictive value.
Determining dynamic adhesion of CD4 T cells to MAdCAM-1 and the in vitro response to vedolizumab before treatment initiation or dynamic integrin regulation in the early course of treatment seem to be promising tools to predict the clinical response to vedolizumab therapy. Larger prospective studies are warranted.
虽然治疗炎症性肠病（IBD）的治疗选择越来越多，但在许多情况下，合理治疗决策的证据仍然缺乏。特别是，目前缺乏预测抗α4β7 整合素抗体 vedolizumab 反应的适当生物标志物。
我们进行了一项队列研究，纳入了 21 名患有溃疡性结肠炎（UC）的患者，这些患者首次接受 vedolizumab 治疗。从外周血中分离 CD4 T 细胞，在体外进行动态黏附重组黏膜血管地址素细胞黏附分子（MAdCAM-）-1，以及体外 vedolizumab 对这种黏附的影响。通过流式细胞术定量测定外周血 CD4 T 细胞上的 α4β1 整合素表达。回顾电子病历以确定对 vedolizumab 的临床反应。
外周血 CD4 T 细胞对 MAdCAM-1 的动态黏附以及体外 vedolizumab 治疗后黏附的减少在 vedolizumab 应答者和非应答者中更高，且 CD4 T 细胞上 α4β1 表达的变化也不同。应答者可以通过高特异性和阳性预测值来识别。
在治疗开始前确定 CD4 T 细胞对 MAdCAM-1 的动态黏附以及对 vedolizumab 的体外反应，或在治疗早期确定整合素的动态调节，似乎是预测 vedolizumab 治疗临床反应的有前途的工具。需要进行更大规模的前瞻性研究。
