α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis

Melde M, Müller T, Schneider IHF, Geppert CI, Mühl L, Besendorf L, Allner C, Becker E, Atreya I, Vitali F, Atreya R, Neurath M, Zundler S (2021)

Publication Type: Journal article

Publication year: 2021

Journal

Therapeutic Advances in Gastroenterology SAGE Publications

Book Volume: 14

DOI: 10.1177/17562848211054707

Abstract

Background: The anti-α4β7 integrin antibody vedolizumab is an established therapeutic option for the treatment of inflammatory bowel disease (IBD). It has also been successfully used in patients with chronic antibiotic-refractory pouchitis following proctocolectomey with ileal pouch-anal anastomosis. However, the expression and function of gut-homing markers as well as strategies to predict the response to vedolizumab in pouchitis are understudied so far. Methods: We used flow cytometry and dynamic adhesion assays to study the expression and function of gut-homing integrins on T cells from patients with pouchitis and controls as well as longitudinally during therapy of pouchitis with vedolizumab. Moreover, we describe clinical effects of vedolizumab in a cohort of patients with pouchitis. Results: T cells from patients with pouchitis express a specific profile of gut-homing integrins. Integrin α4β7 on T cells from patients with pouchitis mediates adhesion to mucosal addressin cell adhesion molecule (MAdCAM)-1, which can be blocked by vedolizumab in vitro. Vedolizumab efficiently treats pouchitis in a portion of patients and response correlates with dynamic adhesion profiles to MAdCAM-1. Conclusion: Our data suggest that T cell trafficking seems to be important for the pathogenesis of pouchitis and support the therapeutic use of vedolizumab. Integrin function might serve as a biomarker to predict response to vedolizumab.

Authors with CRIS profile

Tanja Müller Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Ignaz Hans Friedrich Schneider Medizinische Fakultät Carol-Immanuel Geppert Institute of Pathology Laura Mühl Lehrstuhl für Innere Medizin I Laura Besendorf Medizinische Fakultät Clarissa Allner Lehrstuhl für Innere Medizin I Emily Becker Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Imke Atreya Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Francesco Vitali Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Raja Atreya Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur) Markus Neurath Lehrstuhl für Innere Medizin I Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

How to cite

APA:

Melde, M., Müller, T., Schneider, I.H.F., Geppert, C.-I., Mühl, L., Besendorf, L.,... Zundler, S. (2021). α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis. Therapeutic Advances in Gastroenterology, 14. https://doi.org/10.1177/17562848211054707

MLA:

Melde, Michaela, et al. "α4β7 integrin-dependent adhesion of T cells to MAdCAM-1 is blocked by vedolizumab in patients with chronic refractory pouchitis." Therapeutic Advances in Gastroenterology 14 (2021).

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