Disease-specific B cell clones are shared between patients with Crohn’s disease

Abstract B cells have important functions in gut homeostasis, and dysregulated B cell populations are frequently observed in patients with inflammatory bowel diseases, including both ulcerative colitis (UC) and Crohn’s disease (CD). How these B cell perturbations contribute to disease remains largel...

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Main Authors: Prasanti Kotagiri, William M. Rae, Laura Bergamaschi, Diana Pombal, Ji-Yeun Lee, Nurulamin M. Noor, Raoul S. Sojwal, Samuel J. S. Rubin, Lukas W. Unger, Sofie H. Tolmeijer, Giulia Manferrari, Rachael J. M. Bashford-Rogers, David B. Bingham, Anton Stift, Stephan Rogalla, John Gubatan, James C. Lee, Kenneth G. C. Smith, Eoin F. McKinney, Scott D. Boyd, Paul A. Lyons
Format: Article
Language:English
Published: Nature Portfolio 2025-04-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-58977-y
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author Prasanti Kotagiri
William M. Rae
Laura Bergamaschi
Diana Pombal
Ji-Yeun Lee
Nurulamin M. Noor
Raoul S. Sojwal
Samuel J. S. Rubin
Lukas W. Unger
Sofie H. Tolmeijer
Giulia Manferrari
Rachael J. M. Bashford-Rogers
David B. Bingham
Anton Stift
Stephan Rogalla
John Gubatan
James C. Lee
Kenneth G. C. Smith
Eoin F. McKinney
Scott D. Boyd
Paul A. Lyons
author_facet Prasanti Kotagiri
William M. Rae
Laura Bergamaschi
Diana Pombal
Ji-Yeun Lee
Nurulamin M. Noor
Raoul S. Sojwal
Samuel J. S. Rubin
Lukas W. Unger
Sofie H. Tolmeijer
Giulia Manferrari
Rachael J. M. Bashford-Rogers
David B. Bingham
Anton Stift
Stephan Rogalla
John Gubatan
James C. Lee
Kenneth G. C. Smith
Eoin F. McKinney
Scott D. Boyd
Paul A. Lyons
author_sort Prasanti Kotagiri
collection DOAJ
description Abstract B cells have important functions in gut homeostasis, and dysregulated B cell populations are frequently observed in patients with inflammatory bowel diseases, including both ulcerative colitis (UC) and Crohn’s disease (CD). How these B cell perturbations contribute to disease remains largely unknown. Here, we perform deep sequencing of the B cell receptor (BCR) repertoire in four cohorts of patients with CD, together with healthy controls and patients with UC. We identify BCR clones that are shared between patients with CD but not found in healthy individuals nor in patients with UC, indicating CD-associated B cell immune responses. Shared clones are present in the inflamed gut mucosa, draining intestinal lymph nodes and blood, suggesting the presence of common CD-associated antigens that drive B cell responses in CD patients.
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spelling doaj-art-9c7b7d6013a040bfa33c1f92165d22e12025-08-20T02:28:09ZengNature PortfolioNature Communications2041-17232025-04-0116111310.1038/s41467-025-58977-yDisease-specific B cell clones are shared between patients with Crohn’s diseasePrasanti Kotagiri0William M. Rae1Laura Bergamaschi2Diana Pombal3Ji-Yeun Lee4Nurulamin M. Noor5Raoul S. Sojwal6Samuel J. S. Rubin7Lukas W. Unger8Sofie H. Tolmeijer9Giulia Manferrari10Rachael J. M. Bashford-Rogers11David B. Bingham12Anton Stift13Stephan Rogalla14John Gubatan15James C. Lee16Kenneth G. C. Smith17Eoin F. McKinney18Scott D. Boyd19Paul A. Lyons20Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeDepartment of Medicine, University of Cambridge School of Clinical MedicineDepartment of Pathology, Stanford UniversityDepartment of Medicine, University of Cambridge School of Clinical MedicineDivision of Gastroenterology and Hepatology, Stanford UniversityDivision of Gastroenterology and Hepatology, Stanford UniversityCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeDepartment of Medicine, University of Cambridge School of Clinical MedicineDepartment of Medicine, University of Cambridge School of Clinical MedicineDepartment of Medicine, University of Cambridge School of Clinical MedicineDepartment of Pathology, Stanford UniversityDivision of Visceral Surgery, Department of General Surgery, Medical University of ViennaDivision of Gastroenterology and Hepatology, Stanford UniversityDivision of Gastroenterology and Hepatology, Stanford UniversityCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeDepartment of Pathology, Stanford UniversityCambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of CambridgeAbstract B cells have important functions in gut homeostasis, and dysregulated B cell populations are frequently observed in patients with inflammatory bowel diseases, including both ulcerative colitis (UC) and Crohn’s disease (CD). How these B cell perturbations contribute to disease remains largely unknown. Here, we perform deep sequencing of the B cell receptor (BCR) repertoire in four cohorts of patients with CD, together with healthy controls and patients with UC. We identify BCR clones that are shared between patients with CD but not found in healthy individuals nor in patients with UC, indicating CD-associated B cell immune responses. Shared clones are present in the inflamed gut mucosa, draining intestinal lymph nodes and blood, suggesting the presence of common CD-associated antigens that drive B cell responses in CD patients.https://doi.org/10.1038/s41467-025-58977-y
spellingShingle Prasanti Kotagiri
William M. Rae
Laura Bergamaschi
Diana Pombal
Ji-Yeun Lee
Nurulamin M. Noor
Raoul S. Sojwal
Samuel J. S. Rubin
Lukas W. Unger
Sofie H. Tolmeijer
Giulia Manferrari
Rachael J. M. Bashford-Rogers
David B. Bingham
Anton Stift
Stephan Rogalla
John Gubatan
James C. Lee
Kenneth G. C. Smith
Eoin F. McKinney
Scott D. Boyd
Paul A. Lyons
Disease-specific B cell clones are shared between patients with Crohn’s disease
Nature Communications
title Disease-specific B cell clones are shared between patients with Crohn’s disease
title_full Disease-specific B cell clones are shared between patients with Crohn’s disease
title_fullStr Disease-specific B cell clones are shared between patients with Crohn’s disease
title_full_unstemmed Disease-specific B cell clones are shared between patients with Crohn’s disease
title_short Disease-specific B cell clones are shared between patients with Crohn’s disease
title_sort disease specific b cell clones are shared between patients with crohn s disease
url https://doi.org/10.1038/s41467-025-58977-y
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