Similar Inhibition of Dynamic Adhesion of Lymphocytes From IBD Patients to MAdCAM-1 by Vedolizumab and Etrolizumab-s

Inflamm Bowel Dis. 2018 May 18;24(6):1237-1250. doi: 10.1093/ibd/izy077.

Abstract

Background: Although anti-adhesion therapies are a novel mainstay in the treatment of inflammatory bowel diseases (IBDs), the mechanisms controlling integrin-dependent gut homing are poorly elucidated, and the available techniques for translational functional investigations are limited.

Methods: We used dynamic adhesion assays to study adhesion of CD4+ T cells, CD8+ T cells, CD19+ B cells, and granulocytes to the addressins MAdCAM-1, VCAM-1, and ICAM-1. The effects of vedolizumab, natalizumab, etrolizumab-s, anti-CD11a, and anti-CD18 antibodies were explored.

Results: Adhesion of peripheral blood leukocytes from IBD patients and control donors could be validly assessed, and integrin-mediated addressin adhesion could be specifically inhibited by anti-integrin antibodies. Numbers of adhering cells were partly, but not completely, related to integrin expression. Vedolizumab and etrolizumab-s resulted in similar reduction of adhesion to MAdCAM-1, and preliminary data proposed an association of dynamic adhesion to MAdCAM-1 with response to vedolizumab therapy.

Conclusions: Dynamic adhesion assays are an easy and broadly applicable method for IBD research that is useful for future translational studies and potentially also for supporting clinical treatment decisions. 10.1093/ibd/izy077_video1izy077_Video_15786486962001.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • B-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • Case-Control Studies
  • Cell Adhesion / drug effects
  • Cell Adhesion Molecules
  • Cells, Cultured
  • Granulocytes / drug effects
  • Humans
  • Immunoglobulins / metabolism*
  • Inflammatory Bowel Diseases / drug therapy*
  • Integrins / metabolism
  • Intercellular Adhesion Molecule-1 / metabolism
  • Leukocytes / drug effects*
  • Mucoproteins / metabolism*
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antibodies, Monoclonal, Humanized
  • Cell Adhesion Molecules
  • Immunoglobulins
  • Integrins
  • MADCAM1 protein, human
  • Mucoproteins
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • vedolizumab
  • etrolizumab