Effect of tumor necrosis factor-a blockade on mucosal addressin cell-adhesion molecule-1 in Crohn's disease

Paolo Biancheri, Antonio Di Sabatino, Laura Rovedatti, Paolo Giuffrida, Sandra A. Calarota, Stefania Vetrano, Francesca Vidali, Alessandra Pasini, Silvio Danese, Gino R. Corazza, Thomas T. MacDonald

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Mucosal addressin cell-adhesion molecule (MAdCAM)-1, which is overexpressed on gut endothelium in active Crohn's disease (CD), promotes intestinal recruitment of integrin a4b7 + T cells that sustain chronic inflammation. As tumor necrosis factor alpha (TNF)-a, a cytokine centrally involved in CD, modulates gut endothelial adhesion molecules, we here explored the in vivo and ex vivo effects of TNF-a blockade on MAdCAM-1 expression in CD. Methods: MAdCAM-1 was determined by immunoblotting in colonic biopsies collected before and 10 weeks after either infliximab or adalimumab treatment in CD patients, and in CD biopsies incubated with either infliximab or adalimumab or control IgG1. Integrin b7 + circulating T cells were analyzed by flow cytometry. Results: MAdCAM-1 significantly decreased after either infliximab or adalimumab treatment in responder but not in nonresponder patients. In parallel, an increase of circulating b7 + T cells was found in responder patients only. A marked downregulation of MAdCAM-1 was observed in CD biopsies cultured with either infliximab or adalimumab in comparison to IgG1-treated biopsies. Conclusions: Our findings showing that MAdCAM-1 is downregulated by TNF-a blockade point to a novel mechanism of action of anti-TNFa antibodies in CD.

Original languageEnglish
Pages (from-to)259-264
Number of pages6
JournalInflammatory Bowel Diseases
Volume19
Issue number2
DOIs
Publication statusPublished - Feb 2013

Keywords

  • Adalimumab
  • Gut homing
  • Inflammatory bowel disease
  • Infliximab
  • Integrin

ASJC Scopus subject areas

  • Gastroenterology
  • Immunology and Allergy

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