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

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Item Type:	Article
Title:	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
Creators Name:	Horn, V., Cancino, C.A., Steinheuer, L.M., Obermayer, B., Fritz, K., Nguyen, A.L., Juhran, K.S., Plattner, C., Bösel, D., Oldenburg, L., Burns, M., Schulz, A.R., Saliutina, M., Mantzivi, E., Lissner, D., Conrad, T., Mashreghi, M.F., Zundler, S., Sonnenberg, E., Schumann, M., Haag, L.M., Beule, D., Flatz, L., Trjanoski, Z., D'Haens, G., Weidinger, C., Mei, H.E., Siegmund, B., Thurley, K. and Hegazy, A.N.
Abstract:	BACKGROUND AND AIMS: Despite the success of biological therapies in treating inflammatory bowel disease (IBD), managing patients remains challenging due to the absence of reliable predictors of therapy response. METHODS: In this study, we prospectively sampled two cohorts of IBD patients receiving the anti-integrin α4β7 antibody vedolizumab. Samples were subjected to mass cytometry, single-cell RNA sequencing, single-cell V(D)J sequencing, serum proteomics, and multidimensional flow cytometry to comprehensively assess vedolizumab-induced immunological 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 non-responders prior to treatment compared with responders. This predictive T cell signature demonstrated an activated Th1/Th17 phenotype and exhibited elevated levels of integrin α4β1, potentially making these cells less susceptible to direct targeting by vedolizumab. CONCLUSION: These findings provide a reliable predictive classifier with significant implications for personalized IBD management.
Keywords:	Inflammatory Bowel Disease, Cell Migration and Homing, Integrin a4ß7, CD4+ Memory T Cells, Vedolizumab, Single Cell Profiling, Machine Learning, Therapy Response
Source:	Gastroenterology
ISSN:	0016-5085
Publisher:	Elsevier
Date:	28 September 2024
Additional Information:	Leif S.-H. Ludwig is a member of the TRR241 IBDome Consortium
Official Publication:	https://doi.org/10.1053/j.gastro.2024.09.021
PubMed:	View item in PubMed

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