Multimodal profiling of peripheral blood identifies proliferating circulating effector CD4

CD4(+) memory T cells Inflammatory bowel disease cell migration and homing integrin α4β7 machine learning single cell profiling therapy response vedolizumab

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
27 Sep 2024
Historique:
received: 19 12 2023
revised: 06 09 2024
accepted: 18 09 2024
medline: 30 9 2024
pubmed: 30 9 2024
entrez: 29 9 2024
Statut: aheadofprint

Résumé

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. 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. 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 These findings provide a reliable predictive classifier with significant implications for personalized IBD management.

Sections du résumé

BACKGROUND AND AIMS OBJECTIVE
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 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 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
CONCLUSION CONCLUSIONS
These findings provide a reliable predictive classifier with significant implications for personalized IBD management.

Identifiants

DOI: 10.1053/j.gastro.2024.09.021 PMID: 39343250
pubmed: 39343250
pii: S0016-5085(24)05527-6
doi: 10.1053/j.gastro.2024.09.021
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Investigateurs

Imke Atreya (I)
Raja Atreya (R)
Petra Bacher (P)
Christoph Becker (C)
Christian Bojarski (C)
Nathalie Britzen-Laurent (N)
Caroline Bosch-Voskens (C)
Hyun-Dong Chang (HD)
Andreas Diefenbach (A)
Claudia Günther (C)
Kai Hildner (K)
Christoph S N Klose (CSN)
Kristina Koop (K)
Susanne Krug (S)
Anja A Kühl (AA)
Moritz Leppkes (M)
Rocío López-Posadas (R)
Leif S-H Ludwig (LS)
Clemens Neufert (C)
Markus Neurath (M)
Jay Patankar (J)
Magdalena Prüß (M)
Andreas Radbruch (A)
Chiara Romagnani (C)
Francesca Ronchi (F)
Ashley Sanders (A)
Alexander Scheffold (A)
Jörg-Dieter Schulzke (JD)
Michael Schumann (M)
Sebastian Schürmann (S)
Britta Siegmund (B)
Michael Stürzl (M)
Zlatko Trajanoski (Z)
Antigoni Triantafyllopoulou (A)
Maximilian Waldner (M)
Carl Weidinger (C)
Stefan Wirtz (S)
Sebastian Zundler (S)

Informations de copyright

Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.

Auteurs

Veronika Horn (V)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Camila A Cancino (CA)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Lisa Maria Steinheuer (LM)

Institute for Experimental Oncology, Biomathematics Division, University Hospital Bonn, Bonn, Germany.

Benedikt Obermayer (B)

Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Academy, Clinician Scientist Program, 10178 Berlin, Germany.

Konstantin Fritz (K)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Anke L Nguyen (AL)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Department of Gastroenterology, Central Clinical School, Monash University and Alfred Health, Melbourne, Australia.

Kim Susan Juhran (KS)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Christina Plattner (C)

Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Diana Bösel (D)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Lotte Oldenburg (L)

Department of Gastroenterology, Amsterdam University Medical Centers, De Boelelaan 1117, HV 1081, Amsterdam, The Netherlands.

Marie Burns (M)

Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Axel Ronald Schulz (AR)

Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Mariia Saliutina (M)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Eleni Mantzivi (E)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Donata Lissner (D)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Thomas Conrad (T)

Genomics Technology Platform, Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), 13125, Berlin, Germany; Core Unit Genomics, Berlin Institute of Health at Charité - Universitätsmedizin Berlin, 10178, Berlin, Germany.

Mir-Farzin Mashreghi (MF)

Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Sebastian Zundler (S)

Department of Medicine 1, University Hospital Erlangen and Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany.

Elena Sonnenberg (E)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Michael Schumann (M)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Lea-Maxie Haag (LM)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Dieter Beule (D)

Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Bioinformatics, 10117 Berlin, Germany.

Lukas Flatz (L)

Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland; Department of Dermatology, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.

Zlatko Trjanoski (Z)

Biocenter, Division of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria.

Geert D'Haens (G)

Department of Gastroenterology, Amsterdam University Medical Centers, De Boelelaan 1117, HV 1081, Amsterdam, The Netherlands.

Carl Weidinger (C)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Henrik E Mei (HE)

Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany.

Britta Siegmund (B)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany.

Kevin Thurley (K)

Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany; Institute for Experimental Oncology, Biomathematics Division, University Hospital Bonn, Bonn, Germany.

Ahmed N Hegazy (AN)

Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, 12203 Berlin, Germany; Deutsches Rheuma-Forschungszentrum, ein Institut der Leibniz-Gemeinschaft, 10117 Berlin, Germany; Berlin Institute of Health at Charité - Universitätsmedizin Berlin, BIH Academy, Clinician Scientist Program, 10178 Berlin, Germany. Electronic address: ahmed.hegazy@charite.de.

Classifications MeSH