Abstract
Vedolizumab, a gut-specific biological treatment for inflammatory bowel disease (IBD), is an antibody that binds to the α4β7 integrin and blocks T-cell migration into intestinal mucosa. We aimed to investigate chemokine levels in serum of IBD-patients treated with vedolizumab. In this pilot study, we included 11 IBD patients (8 Crohn’s disease, 3 ulcerative colitis) previously non-respondent to anti-tumor necrosis factor (TNF)-agents. Patients received vedolizumab at week 0, 2 and 6 and were evaluated for clinical efficacy at week 10. Clinical characteristics and routine laboratory parameters were obtained and patients were classified as responders or non-responders. Expression of 21 chemokines in serum was measured using Proximity Extension Assay and related to clinical outcome. At week 10, 6 out of 11 patients had clinically responded. Overall expression of CCL13 increased after treatment. In non-responders, expression of CCL13 and CXCL8 increased after treatment, and CCL20 and CXCL1 expressions were higher compared to responders. In responders, CCL28 decreased after treatment. C-reactive protein (CRP) correlated negatively with 6 chemokines before therapy, but not after therapy. Systemic CCL13 expression increases in IBD-patients after vedolizumab therapy and several chemokine levels differ between responders and non-responders. An increased CCL13-level when starting vedolizumab treatment, might indicate potential prognostic value of measuring chemokine levels when starting therapy with vedolizumab. This study provides new information on modulation of systemic chemokine levels after vedolizumab treatment.
Highlights
Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the intestine and primarily includes ulcerative colitis (UC), Crohn’s disease (CD), and IBD-unclassified
To reach the site of inflammation, circulating leukocytes migrate through the endothelium in highly controlled processes, where in the interaction between integrins expressed on effector cells and adhesion molecules expressed on endothelial cells is crucial; in such interactions the effector cells migrate with a high degree of specificity
When we analyzed chemokine levels according to clinical response, we found that responding patients exhibited decreased levels of CCL28 after treatment
Summary
Inflammatory bowel disease (IBD) is a group of chronic inflammatory diseases of the intestine and primarily includes ulcerative colitis (UC), Crohn’s disease (CD), and IBD-unclassified. CC chemokines are mainly responsible for the recruitment of lymphocytes, whereas CXC chemokines have the highest ability to attract neutrophils and monocytes [8,9]. Besides the recruitment of effector cells, chemokines are involved in the adhesion and migration of leukocytes across the endothelium [9,10]. To reach the site of inflammation, circulating leukocytes migrate through the endothelium in highly controlled processes, where in the interaction between integrins expressed on effector cells and adhesion molecules expressed on endothelial cells is crucial; in such interactions the effector cells migrate with a high degree of specificity. In total 14 integrin combinations are described to regulate immune cell traffic in humans [11,12,13]. The specificity of the adhesion molecules differs, whereas vascular cell adhesion molecule 1 (VCAM-1) is expressed in the gut and the brain, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is only expressed in the intestine [14]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
