Gut-Associated Lymphoid Tissue Attrition Is Associated With Response to Anti-α4β7 Therapy in Patients With Ulcerative Colitis
abstract
This abstract is available on the publisher's site.
Access this abstract nowVedolizumab (VDZ) is a first-line treatment in ulcerative colitis (UC) that targets the α4β7- mucosal vascular addressin cell adhesion molecule 1 (MAdCAM-1) axis. To determine the mechanisms of action of VDZ, we examined five distinct cohorts of patients with UC. A decrease in naïve B and T cells in the intestines and gut-homing (β7+) plasmablasts in circulation of VDZ-treated patients suggested that VDZ targets gut-associated lymphoid tissue (GALT). Anti-α4β7 blockade in wild-type and photoconvertible (KikGR) mice confirmed a loss of GALT size and cellularity because of impaired cellular entry. In VDZ-treated patients with UC, treatment responders demonstrated reduced intestinal lymphoid aggregate size and follicle organization and a reduction of β7+IgG+ plasmablasts in circulation, as well as IgG+ plasma cells and FcγR-dependent signaling in the intestine. GALT targeting represents a previously unappreciated mechanism of action of α4β7-targeted therapies, with major implications for this therapeutic paradigm in UC.
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Gut-associated lymphoid tissue attrition associates with response to anti-α4β7 therapy in ulcerative colitis
Sci Immunol 2024 Apr 19;9(94)eadg7549, P Canales-Herrerias, M Uzzan, A Seki, RS Czepielewski, B Verstockt, AE Livanos, F Raso, A Dunn, D Dai, A Wang, Z Al-Taie, J Martin, T Laurent, HM Ko, M Tokuyama, M Tankelevich, H Meringer, F Cossarini, D Jha, A Krek, JD Paulsen, MD Taylor, MZ Nakadar, J Wong, EC Erlich, RL Mintz, EJ Onufer, BA Helmink, K Sharma, A Rosenstein, D Ganjian, G Chung, T Dawson, J Juarez, V Yajnik, A Cerutti, JJ Faith, M Suarez-Farinas, C Argmann, F Petralia, GJ Randolph, AD Polydorides, A Reboldi, JF Colombel, S MehandruFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.