Besendorf Laura, Müller Tanja M, Geppert Carol-Immanuel, Schneider Ines, Mühl Laura, Atreya Imke, Vitali Francesco, Atreya Raja, Neurath Markus F, Zundler Sebastian
Department of Medicine 1, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
Therap Adv Gastroenterol. 2022 Jun 28;15:17562848221098899. doi: 10.1177/17562848221098899. eCollection 2022.
In Crohn's disease and ulcerative colitis, the anti-α4β7 integrin antibody vedolizumab has demonstrated efficacy in phase III trials and has been successfully used under real-world conditions. Occasionally, it has also been used in other forms of inflammatory bowel disease (IBD) such as microscopic colitis (MC). However, the mechanisms of vedolizumab in MC have not been studied to date. Therefore, we aimed to investigate the expression and functional role of gut-homing integrins and in particular α4β7 integrin in a cohort study in MC.
We studied the expression of gut homing integrins on T cells from patients with MC and healthy controls by flow cytometry. To investigate the function of α4β7 integrin in MC and the potential of vedolizumab to block it, we used dynamic adhesion assays and transmigrations assays. Moreover, we describe two clinical cases of MC patients treated with vedolizumab.
A specific profile of gut homing markers can be found on T cells from patients with MC. α4β7 integrin functionally leads to firm adhesion to MAdCAM-1 and supports transmigration. Vedolizumab is able to block both processes. In two cases of MC, we observed reduced clinical symptoms and histologic improvement upon therapy with vedolizumab.
Our data suggest that α4β7 mediates gut homing of T cells also in MC and that, on single cell level, vedolizumab blocks the function of α4β7 in MC. Thus, we provide mechanistic evidence supporting vedolizumab as promising therapeutic option for MC.
在克罗恩病和溃疡性结肠炎中，抗α4β7整合素抗体维多珠单抗在III期试验中已显示出疗效，并已在实际临床中成功应用。偶尔，它也被用于其他形式的炎症性肠病（IBD），如显微镜下结肠炎（MC）。然而，迄今为止，维多珠单抗在MC中的作用机制尚未得到研究。因此，我们旨在通过一项队列研究，探究肠道归巢整合素尤其是α4β7整合素在MC中的表达及功能作用。
我们通过流式细胞术研究了MC患者和健康对照者T细胞上肠道归巢整合素的表达。为了研究α4β7整合素在MC中的功能以及维多珠单抗阻断其功能的潜力，我们使用了动态黏附试验和迁移试验。此外，我们描述了两例接受维多珠单抗治疗的MC患者的临床病例。
在MC患者的T细胞上可以发现肠道归巢标志物的特定表达谱。α4β7整合素在功能上导致与黏膜地址素细胞黏附分子-1（MAdCAM-1）的牢固黏附，并支持迁移。维多珠单抗能够阻断这两个过程。在两例MC患者中，我们观察到维多珠单抗治疗后临床症状减轻且组织学改善。
我们的数据表明，α4β7在MC中也介导T细胞的肠道归巢，并且在单细胞水平上，维多珠单抗可阻断MC中α4β7的功能。因此，我们提供了机制证据，支持维多珠单抗作为MC的一种有前景的治疗选择。
