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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 & 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. |
| Keywords: | Inflammatory Bowel Disease, Cell Migration and Homing, Integrin α4β7, CD4+ Memory T Cells, Vedolizumab, Single Cell Profiling, Machine Learning, Therapy Response |
| Source: | Gastroenterology |
| ISSN: | 0016-5085 |
| Publisher: | Elsevier |
| Volume: | 168 |
| Number: | 2 |
| Page Range: | 327-343 |
| Date: | February 2025 |
| 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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