Vedolizumab blocks alpha 4 beta 7 integrin-mediated T cell adhesion to MAdCAM-1 in microscopic colitis

Background: In Crohn's disease and ulcerative colitis, the anti-alpha 4 beta 7 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 alpha 4 beta 7 integrin in a cohort study in MC. Methods: 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 alpha 4 beta 7 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. Results: A specific profile of gut homing markers can be found on T cells from patients with MC. alpha 4 beta 7 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. Conclusion: Our data suggest that alpha 4 beta 7 mediates gut homing of T cells also in MC and that, on single cell level, vedolizumab blocks the function of alpha 4 beta 7 in MC. Thus, we provide mechanistic evidence supporting vedolizumab as promising therapeutic option for MC.