Article
作者: Chang, Hyun-Dong ; Trjanoski, Zlatko ; Cancino, Camila A. ; Beule, Dieter ; Romagnani, Chiara ; Bösel, Diana ; Triantafyllopoulou, Antigoni ; Mashreghi, Mir-Farzin ; Schulz, Axel Ronald ; Neurath, Markus ; Sanders, Ashley ; Prüß, Magdalena ; Oldenburg, Lotte ; Patankar, Jay ; Koop, Kristina ; Atreya, Imke ; Bosch-Voskens, Caroline ; Scheffold, Alexander ; Britzen-Laurent, Nathalie ; Krug, Susanne ; Schürmann, Sebastian ; Stürzl, Michael ; Juhran, Kim Susan ; Kühl, Anja A. ; Neufert, Clemens ; Burns, Marie ; Mantzivi, Eleni ; Ludwig, Leif S.-H. ; Thurley, Kevin ; Nguyen, Anke L ; D'Haens, Geert ; Siegmund, Britta ; Weidinger, Carl ; Mei, Henrik E. ; Wirtz, Stefan ; Saliutina, Mariia ; Schulzke, Jörg-Dieter ; Günther, Claudia ; Steinheuer, Lisa Maria ; Fritz, Konstantin ; Diefenbach, Andreas ; López-Posadas, Rocío ; Waldner, Maximilian ; Flatz, Lukas ; Sonnenberg, Elena ; Conrad, Thomas ; Horn, Veronika ; Leppkes, Moritz ; Becker, Christoph ; Hildner, Kai ; Hegazy, Ahmed N ; Siegmund, Britta ; Cancino, Camila A ; Hegazy, Ahmed N. ; Radbruch, Andreas ; Zundler, Sebastian ; Plattner, Christina ; Ronchi, Francesca ; Lissner, Donata ; Bacher, Petra ; Trjanoski, Zlatko ; Trajanoski, Zlatko ; Klose, Christoph S.N. ; Bojarski, Christian ; Nguyen, Anke L. ; D’Haens, Geert ; Weidinger, Carl ; Mei, Henrik E ; Thurley, Kevin ; Haag, Lea-Maxie ; Obermayer, Benedikt ; Schumann, Michael ; Atreya, Raja
BACKGROUND AND AIMSDespite 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.METHODSIn 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.RESULTSVedolizumab 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.CONCLUSIONThese findings provide a reliable predictive classifier with significant implications for personalized IBD management.