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

Abstract

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.

Baseline levels of dynamic CD4+ T cell adhesion to MAdCAM-1 correlate with clinical response to vedolizumab treatment in ulcerative colitis: a cohort study

“…However, another study reported that response to vedolizumab was associated with pre-therapeutic composition of the intestinal microbiome [29]. Moreover, we had suggested that dynamic changes in the expression of α4β1 on peripheral blood CD4 + T cells in the early course of vedolizumab treatment and the baseline dynamic adhesion of CD4 + T cells to MAdCAM-1 in vitro might predict subsequent therapeutic response [17,20].…”

“…Taken together, our data suggest that determining the baseline adhesion of CD4 + T cells to MAdCAM-1 and their response to vedolizumab in vitro with the proposed assay may be suitable as a functional biomarker and help to support treatment decisions in most patients. It is important to mention, thatbased on previous observations [17] differential levels of CD4 + T cell adhesion to MAdCAM-1 are most likely not a result of differential α4β7 integrin expression, but rather differential intrinsic functionality of this pathways in responders vs. nonresponders.…”

“…Dynamic live cell adhesion was analysed as determined previously [17,18]. In brief, the inside of miniature borosilicate capillaries (Vitrocom) was coated with Fc chimera of rhMAdCAM-1 (R&D Systems) at a concentration of 5 μg/mL in 150 mM NaCl with 10 mM HEPES for 1 h at 37°C.…”

“…We had previously introduced a dynamic adhesion assay to study the adhesion of immune cells to cell adhesion molecules [17]. In this context, we had reported the anecdotal observation that the extent of dynamic adhesion of peripheral blood CD4 + T cells from IBD patients to the α4β7 ligand mucosal vascular addressin cell adhesion molecule (MAdCAM-)1 in this assay before initiation of vedolizumab treatment seemed to correlate with subsequent clinical response to therapy.…”

Cellular Mechanisms of Etrolizumab Treatment in Inflammatory Bowel Disease

“…Suspensions of 1.5 million cells/mL in adhesion buffer (pH 7.4, 150 mM NaCl, 10 mM HEPES, 1 mM CaCl 2 , 1 mM MgCl 2 , 1 mM MnCl 2 ) were prepared and etrolizumab-s was added or not to aliquots of so far untreated cells. Capillaries for dynamic in vitro adhesion assays were prepared as previously described (Binder et al, 2018). In brief, miniature borosilicate capillaries (Vitrocom) were coated with 5 μg/mL rhMAdCAM-1-Fc-chimera (R&D Systems) in 150 mM NaCl with 10 mM HEPES for 1 h at 37°C.…”