α4β7 Integrin-dependent Adhesion of T Cells to MAdCAM-1 is Blocked by Vedolizumab in Patients with Chronic Refractory Pouchitis

Overview

Journal Therap Adv Gastroenterol

Publisher Sage Publications

Specialty Gastroenterology

Date 2021 Dec 6

PMID 34868349

Citations 1

Authors

Michaela Melde

Tanja M Muller

Ines Schneider

Carol-Immanuel Geppert

Laura Muhl

Laura Besendorf

Clarissa Allner

Emily Becker

Imke Atreya

Francesco Vitali

Raja Atreya

Markus F Neurath

Sebastian Zundler

Affiliations

Soon will be listed here.

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 . 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.

Citing Articles

The Force-Dependent Mechanism of an Integrin α4β7-MAdCAM-1 Interaction.

Su Y, Luo Z, Sun D, Yang B, Li Q Int J Mol Sci. 2023; 24(22).

PMID: 38003252 PMC: 10670920. DOI: 10.3390/ijms242216062.

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