Expression and function of α4β7 integrin predict the success of vedolizumab treatment in inflammatory bowel disease
Schneider I, Allner C, Mühl L, Melde M, Lissner D, Mantzivi E, Glauben R, Vitali F, Becker E, Atreya I, Müller T, Atreya R, Siegmund B, Neurath M, Zundler S (2022)
Publication Type: Journal article
Publication year: 2022
Journal
DOI: 10.1016/j.trsl.2022.10.003
Abstract
Inflammatory bowel diseases are medically intractable and require constant therapy in many cases. While a growing number of biologicals and small molecules is available for treatment, a substantial portion of patients experiences primary non-response to these compounds and head-to-head evidence for therapy selection is scarce. Thus, approaches to predict treatment success in individual patients are a huge unmet need. We had previously suggested that the expression and function of α4β7 integrin on T cells in the peripheral blood correlate to outcomes of therapy with the anti-α4β7 integrin antibody vedolizumab. Here, we conducted a translational multicenter trial to prospectively evaluate this hypothesis. In a cohort of 89 patients with inflammatory bowel disease undergoing regular therapy with vedolizumab, lower baseline expression of α4β7 was associated with short-term clinical response. Consistently, low α4β7 expression in patients achieving remission predicted sustained remission in week 30. Moreover, high dynamic adhesion of CD4+ T cells to MAdCAM-1 and high reduction of adhesion by vedolizumab in vitro at baseline were associated with clinical remission. These data substantiate the potential of α4β7 integrin function and expression to forecast outcomes of vedolizumab therapy. Further translational efforts are necessary to improve the performance of the assays and to implement the concept in clinical practice.
Authors with CRIS profile
Clarissa Allner
Lehrstuhl für Innere Medizin I
Laura Mühl
Lehrstuhl für Innere Medizin I
Francesco Vitali
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Emily Becker
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Imke Atreya
Medizinische Fakultät
Tanja Müller
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Raja Atreya
Professur für Translationale Immunforschung bei chronisch entzündlichen Darmerkrankungen (Heisenberg-Professur)
Markus Neurath
Lehrstuhl für Innere Medizin I
Sebastian Zundler
Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology
Involved external institutions
Germany (DE)How to cite
APA:
Schneider, I., Allner, C., Mühl, L., Melde, M., Lissner, D., Mantzivi, E.,... Zundler, S. (2022). Expression and function of α4β7 integrin predict the success of vedolizumab treatment in inflammatory bowel disease. Translational Research. https://doi.org/10.1016/j.trsl.2022.10.003
MLA:
Schneider, Ines, et al. "Expression and function of α4β7 integrin predict the success of vedolizumab treatment in inflammatory bowel disease." Translational Research (2022).
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