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

Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, Berlin, Germany; Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin Institute of Health Academy, Clinician Scientist Program, Berlin, Germany. Electronic address:

Published: September 2024

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.

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Source
http://dx.doi.org/10.1053/j.gastro.2024.09.021DOI Listing

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