Deep Analysis of the Peripheral Immune System in IBD Reveals New Insight in Disease Subtyping and Response to Monotherapy or Combination Therapy.


Journal

Cellular and molecular gastroenterology and hepatology
ISSN: 2352-345X
Titre abrégé: Cell Mol Gastroenterol Hepatol
Pays: United States
ID NLM: 101648302

Informations de publication

Date de publication:
2021
Historique:
received: 01 06 2020
revised: 24 03 2021
accepted: 24 03 2021
pubmed: 5 4 2021
medline: 28 1 2022
entrez: 4 4 2021
Statut: ppublish

Résumé

Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations. We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn's disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use. We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs.

Sections du résumé

BACKGROUND
Inflammatory bowel disease (IBD) is a complex disease with variable presentation, progression, and response to therapies. Current disease classification is based on subjective clinical phenotypes. The peripheral blood immunophenome can reflect local inflammation, and thus we measured 39 circulating immune cell types in a large cohort of IBD and control subjects and performed immunotype:phenotype associations.
METHODS
We performed fluorescence-activated cell sorting or CyTOF analysis on blood from 728 Crohn's disease, 464 ulcerative colitis, and 334 non-IBD patients, with available demographics, endoscopic and clinical examinations and medication use.
RESULTS
We observed few immune cell types commonly affected in IBD (lowered natural killer cells, B cells, and CD45RA
CONCLUSIONS
We present a peripheral map of immune cell changes in IBD related to disease entity and therapies as a resource for hypothesis generation. We propose the changes in B cell subsets could affect antibody formation and potentially explain the mechanism behind the superiority of combination therapy through the impact of thiopurines on pharmacokinetics of anti-TNFs.

Identifiants

pubmed: 33813036
pii: S2352-345X(21)00064-3
doi: 10.1016/j.jcmgh.2021.03.012
pmc: PMC8263768
pii:
doi:

Substances chimiques

Tumor Necrosis Factor-alpha 0
Mercaptopurine E7WED276I5

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

599-632

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Auteurs

Roman Kosoy (R)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York.

Seunghee Kim-Schulze (S)

Hematology and Medical Oncology, Icahn School of Medicine at Mount Sinai, New York, New York; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Adeeb Rahman (A)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Joshua R Friedman (JR)

Alnylam Pharmaceuticals, Boston, Massachusetts.

Ruiqi Huang (R)

Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.

Lauren A Peters (LA)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York; Sema4, Stamford, Connecticut.

El-Ad Amir (EA)

Astrolabe Diagnostics, Fort Lee, New Jersey.

Jacqueline Perrigoue (J)

Janssen R&D, Spring House, Pennsylvania.

Aleksandar Stojmirovic (A)

Janssen R&D, Spring House, Pennsylvania.

Won-Min Song (WM)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York.

Hao Ke (H)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York.

Ryan Ungaro (R)

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

Saurabh Mehandru (S)

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

Judy Cho (J)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

Marla Dubinsky (M)

Pediatric GI and Hepatology, Icahn School of Medicine at Mount Sinai, New York, New York; Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Mark Curran (M)

Janssen R&D, Spring House, Pennsylvania.

Carrie Brodmerkel (C)

Janssen R&D, Spring House, Pennsylvania.

Eric E Schadt (EE)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York; Sema4, Stamford, Connecticut.

Bruce E Sands (BE)

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York.

Jean-Frederic Colombel (JF)

Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, New York; Susan and Leonard Feinstein IBD Clinical Center, Icahn School of Medicine at Mount Sinai, New York, New York.

Andrew Kasarskis (A)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York; Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York.

Carmen A Argmann (CA)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Icahn Institute for Data Science and Genomic Technology, New York, New York. Electronic address: carmen.argmann@mssm.edu.

Mayte Suárez-Fariñas (M)

Department of Genetics and Genomics, Icahn School of Medicine at Mount Sinai, New York, New York; Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, New York. Electronic address: mayte.suarezfarinas@mssm.edu.

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