Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease.

Horn V, Cancino CA, Steinheuer LM, Obermayer B, Fritz K, Nguyen AL, Juhran KS, Plattner C, Bösel D, Oldenburg L, Burns M, Schulz AR, Saliutina M, Mantzivi E, Lissner D, Conrad T, Mashreghi MF, Sonnenberg E, Schumann M, Haag LM, Beule D, Flatz L, Atreya I, Atreya R, Bacher P, Becker C, Bojarski C, Britzen-Laurent N, Bosch-Voskens C, Chang HD, Diefenbach A, Günther C, Hildner K, Klose CS, Koop K, Krug S, Kühl AA, Leppkes M, Lopez Posadas R, Ludwig LS, Neufert C, Neurath M, Patankar J, Prüß M, Radbruch A, Romagnani C, Ronchi F, Sanders A, Scheffold A, Schulzke JD, Schürmann S, Stürzl M, Triantafyllopoulou A, Waldner M, Wirtz S, Zundler S, Trajanoski Z, D'Haens G, Weidinger C, Mei HE, Siegmund B, Thurley K, Hegazy AN (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Gastroenterology Elsevier

Book Volume: 168

Pages Range: 327-343

Journal Issue: 2

DOI: 10.1053/j.gastro.2024.09.021

Abstract

BACKGROUND & AIMS: Despite the success of biological therapies in treating inflammatory bowel disease, managing patients remains challenging due to the absence of reliable predictors of therapy response. METHODS: In this study, we prospectively sampled 2 cohorts of patients with inflammatory bowel disease receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry; single-cell RNA sequencing; single-cell B and T cell receptor sequencing (BCR/TCR-seq); serum proteomics; and multiparametric flow cytometry to comprehensively assess vedolizumab-induced immunologic changes in the peripheral blood and their potential associations with treatment response. RESULTS: Vedolizumab treatment led to substantial alterations in the abundance of circulating immune cell lineages and modified the T-cell receptor diversity of gut-homing CD4+ memory T cells. Through integration of multimodal parameters and machine learning, we identified a significant increase in proliferating CD4+ memory T cells among nonresponders before treatment compared with responders. This predictive T-cell signature demonstrated an activated T-helper 1/T-helper 17 cell phenotype and exhibited elevated levels of integrin α4β1, potentially making these cells less susceptible to direct targeting by vedolizumab. CONCLUSIONS: These findings provide a reliable predictive classifier with significant implications for personalized inflammatory bowel disease management.

Authors with CRIS profile

Christoph Becker Professur für Molekulare Gastroenterologie Nathalie Britzen-Laurent Medizinische Fakultät Caroline Bosch-Voskens Department of Dermatology Claudia Günther Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Kai Hildner Juniorprofessur für Pneumologie/Immunologie Kristina Koop Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Moritz Leppkes Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Rocío Lopez Posadas Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Clemens Neufert Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Markus Neurath Lehrstuhl für Innere Medizin I (Medizin 1) Jay Patankar Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Sebastian Schürmann Lehrstuhl für Medizinische Biotechnologie (MBT) Michael Stürzl Professur für Molekulare und Experimentelle Chirurgie Maximilian Waldner Professur für Funktionelle Bildgebung in der Medizin Stefan Wirtz Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology Sebastian Zundler Department of Medicine 1 – Gastroenterology, Pneumology and Endocrinology

Involved external institutions

Deutsches Rheuma-Forschungszentrum (DRFZ) DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Berliner Institut für Gesundheitsforschung in der Charité / Berlin Institute of Health at Charité (BIH) DE Germany (DE) Kantonsspital St.Gallen CH Switzerland (CH) Max-Delbrück-Centrum für Molekulare Medizin in der Helmholtz-Gemeinschaft / Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Medizinische Universität Innsbruck AT Austria (AT) Amsterdam University Medical Centers (Amsterdam UMC) / Amsterdam Universitair Medische Centra NL Netherlands (NL) Christian-Albrechts-Universität zu Kiel DE Germany (DE)

How to cite

APA:

Horn, V., Cancino, C.A., Steinheuer, L.M., Obermayer, B., Fritz, K., Nguyen, A.L.,... Hegazy, A.N. (2025). Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease. Gastroenterology, 168(2), 327-343. https://doi.org/10.1053/j.gastro.2024.09.021

MLA:

Horn, Veronika, et al. "Multimodal Profiling of Peripheral Blood Identifies Proliferating Circulating Effector CD4+ T Cells as Predictors for Response to Integrin α4β7-Blocking Therapy in Inflammatory Bowel Disease." Gastroenterology 168.2 (2025): 327-343.

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