TY - JOUR T1 - Vedolizumab is associated with changes in innate rather than adaptive immunity in patients with inflammatory bowel disease JF - Gut JO - Gut DO - 10.1136/gutjnl-2018-316023 SP - gutjnl-2018-316023 AU - Sebastian Zeissig AU - Elisa Rosati AU - C Marie Dowds AU - Konrad Aden AU - Johannes Bethge AU - Berenice Schulte AU - Wei Hung Pan AU - Neha Mishra AU - Maaz Zuhayra AU - Marlies Marx AU - Maren Paulsen AU - Anne Strigli AU - Claudio Conrad AU - Dörthe Schuldt AU - Anupam Sinha AU - Henriette Ebsen AU - Sabin-Christin Kornell AU - Susanna Nikolaus AU - Alexander Arlt AU - Dieter Kabelitz AU - Mark Ellrichmann AU - Ulf Lützen AU - Philip C Rosenstiel AU - Andre Franke AU - Stefan Schreiber Y1 - 2018/05/05 UR - http://gut.bmj.com/content/early/2018/05/05/gutjnl-2018-316023.abstract N2 - Objective Vedolizumab, a monoclonal antibody directed against the integrin heterodimer α4β7, is approved for the treatment of Crohn’s disease and ulcerative colitis. The efficacy of vedolizumab has been suggested to result from inhibition of intestinal T cell trafficking although human data to support this conclusion are scarce. We therefore performed a comprehensive analysis of vedolizumab-induced alterations in mucosal and systemic immunity in patients with inflammatory bowel disease (IBD), using anti-inflammatory therapy with the TNFα antibody infliximab as control.Design Immunophenotyping, immunohistochemistry, T cell receptor profiling and RNA sequencing were performed using blood and colonic biopsies from patients with IBD before and during treatment with vedolizumab (n=18) or, as control, the anti-TNFα antibody infliximab (n=20). Leucocyte trafficking in vivo was assessed using single photon emission computed tomography and endomicroscopy.Results Vedolizumab was not associated with alterations in the abundance or phenotype of lamina propria T cells and did not affect the mucosal T cell repertoire or leucocyte trafficking in vivo. Surprisingly, however, α4β7 antibody treatment was associated with substantial effects on innate immunity including changes in macrophage populations and pronounced alterations in the expression of molecules involved in microbial sensing, chemoattraction and regulation of the innate effector response. These effects were specific to vedolizumab, not observed in response to the TNFα antibody infliximab, and associated with inhibition of intestinal inflammation.Conclusion Our findings suggest that modulation of innate immunity contributes to the therapeutic efficacy of vedolizumab in IBD.Trial registration number NCT02694588 ER -