Projects per year
Abstract
Age-associated B cells (ABCs) are an immune cell subset linked to autoimmunity, infection and ageing, and whose pathophysiological importance was recently highlighted using single cell synovial tissue profiling. To elucidate their pathophysiological relevance, peripheral blood (PB) ABCs from early rheumatoid arthritis (eRA) patients naïve to disease-modifying anti-rheumatic drugs (DMARDs) were compared with their synovial fluid (SF) counterparts, and to PB ABCs from psoriatic arthritis patients and healthy controls. PB and SF B-cell subsets were phenotyped by multi-parameter flow cytometry, sorted and subjected to gene expression profiling (NanoString nCounter® Immunology V2 Panel) and functional characterization (stimulated cytokine measurements by immunoassay). PB ABCs of eRA patients, which are transcriptionally distinct from those of control cohorts, express chemokine receptors and adhesion molecules, such as CXCR3, that favour homing to inflammatory sites over lymphoid tissue. These cells are an activated, class-switched B-cell subset expressing high levels of HLA-DR, co-stimulatory molecules and T-bet. Their secretion profile includes IL-12p70 and IL-23 but low levels of IL-10. High surface expression of FcRL family members, including FcRL3, furthermore suggests a role for these cells in autoimmunity. Finally, and unlike in the periphery where they are rare, ABCs are the predominant B-cell subsets in SF. These observations indicate the predilection of ABCs for inflammatory tissue in RA, where their propensity for antigen presentation and pro-inflammatory phenotype may support autoimmune pathology. Their potential as a therapeutic target therefore warrants further study.
Original language | English |
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Pages (from-to) | 640-653 |
Number of pages | 14 |
Journal | Immunology |
Volume | 168 |
Issue number | 4 |
Early online date | 25 Oct 2022 |
DOIs | |
Publication status | Published - Apr 2023 |
Bibliographical note
Funding Information:The authors gratefully acknowledge the participation of all patients and healthy volunteers. We acknowledge the Flow Cytometry Core Facility at Newcastle University for their expert help. We are very thankful to Professor Satoshi Nagata (National Institutes of Biomedical Innovation, Health and Nutrition, Japan) for his kind gift of the FcRL expression plasmids and anti-FcRL2 antibody, as well as his expert advice and guidance.
This work was funded by the Research into Inflammatory Arthritis Centre Versus Arthritis (RACE) (grant number 22072) and supported by the J.G.W. Patterson Foundation, the EU/EFPIA Innovative Medicines Initiative 2 Joint Undertaking RTCure (grant number 777357) and the National Institute for Health and Care Research (NIHR) Newcastle Biomedical Research Centre (BRC) at the Newcastle Hospitals NHS Foundation Trust and Newcastle University, UK. John D. Isaacs is a NIHR Senior Investigator. The views expressed are those of the author(s) and not necessarily those of the National Institute for Health Research or the Department of Health and Social Care.
Publisher Copyright:
© 2022 The Authors. Immunology published by John Wiley & Sons Ltd.
Keywords
- age-associated B cells
- chemokine receptors
- FcRL family
- rheumatoid arthritis
- transcriptome
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology
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Rheumatoid Arthritis Centre for Excellence (RACE 2)
Filer, A. (Co-Investigator), Lord, J. (Co-Investigator), Raza, K. (Principal Investigator), Scheel-Toellner, D. (Co-Investigator), Anderson, G. (Co-Investigator), Buckley, C. (Co-Investigator), Clark, A. (Co-Investigator) & Falahee, M. (Co-Investigator)
1/04/19 → 30/09/25
Project: Research
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H2020_COLLAB (IMI)_RT CURE
Scheel-Toellner, D. (Co-Investigator), Filer, A. (Co-Investigator), Raza, K. (Co-Investigator), Wraith, D. (Principal Investigator) & Buckley, C. (Co-Investigator)
1/09/17 → 31/08/23
Project: EU