P339 MadCAM1 expression in intestinal lamina propria endothelium varies among inflammatory bowel disease patients

Abstract

Background: Vedolizumab, a monoclonal antibody against α4β7 integrin has been shown to be effective in inducing and maintaining remission in inflammatory bowel disease (IBD). By blocking α4β7, it is preventing the homing of lymphocytes through binding to mucosal vascular adressin cell adhesion molecule 1 (MadCAM1) localised on the intestinal endothelial cells. It is unclear to which extent the gut homing of lymphocytes is subject to redundant biological process involving other pathways than α4β7-MadCAM1 interaction. There are no data on the interindividual variability of MadCAM1 expression that might influence the effect of vedolizumab. The aim of our study was thus first, to determine the expression of MadCAM1 on the intestinal endothelial cells of IBD patients. Second, we aimed to assess the relationship of MadCAM1 expression with the clinical response to vedolizumab. Methods: All IBD patients referred for the treatment with vedolizumab to one referral center were included. The biopsies or resection specimen from the inflamed intestinal tissue were stained by immunohistochemistry for MadCAM1 expression. Clinical response to vedolizumab was assessed in patients with the minimal treatment duration of 10 weeks and the differences in MadCAM1 expression between responders and non-responders were analyzed. Results: In total, 34 IBD patients were referred for vedolizumab treatment; for 21 of them intestinal biopsies or surgical specimen could have been retrieved and stained for MadCAM1 expression. In three out of these 21 patients (14%) no MadCAM1 expression in intestinal endothelium was detected, remaining 18 patients expressed MadCAM1 to various extent (from 30 to 100% of all vessels). Ten patients had the minimal follow-up of 10 weeks of treatment, 4 out of these 10 patients had clinical response to vedolizumab. The only two patients not expressing MadCAM1 in this group were both no responders with the respective follow-up of 16 and 14 weeks of treatment. Conclusions: MadCAM1 expression in intestinal endothelium varies among IBD patients. Other gut homing mechanisms of lymphocytes might thus prevail in some IBD patients and limit the anti-inflammatory effect of vedolizumab.