Single-cell insights into immune dysregulation in rheumatoid arthritis flare versus drug-free remission

Kenneth F. Baker (), David McDonald, Gillian Hulme, Rafiqul Hussain, Jonathan Coxhead, David Swan, Axel R. Schulz, Henrik E. Mei, Lucy MacDonald, Arthur G. Pratt, Andrew Filby, Amy E. Anderson and John D. Isaacs
Additional contact information
Kenneth F. Baker: Newcastle University
David McDonald: Newcastle University
Gillian Hulme: Newcastle University
Rafiqul Hussain: Newcastle University
Jonathan Coxhead: Newcastle University
David Swan: University of Sunderland
Axel R. Schulz: A Leibniz Institute
Henrik E. Mei: A Leibniz Institute
Lucy MacDonald: Glasgow University
Arthur G. Pratt: Newcastle University
Andrew Filby: Newcastle University
Amy E. Anderson: Newcastle University
John D. Isaacs: Newcastle University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: Abstract Immune-mediated inflammatory diseases (IMIDs) are typically characterised by relapsing and remitting flares of inflammation. However, the unpredictability of disease flares impedes their study. Addressing this critical knowledge gap, we use the experimental medicine approach of immunomodulatory drug withdrawal in rheumatoid arthritis (RA) remission to synchronise flare processes allowing detailed characterisation. Exploratory mass cytometry analyses reveal three circulating cellular subsets heralding the onset of arthritis flare – CD45RO+PD1hi CD4+ and CD8+ T cells, and CD27+CD86+CD21- B cells – further characterised by single-cell sequencing. Distinct lymphocyte subsets including cytotoxic and exhausted CD4+ memory T cells, memory CD8+CXCR5+ T cells, and IGHA1+ plasma cells are primed for activation in flare patients. Regulatory memory CD4+ T cells (Treg cells) increase at flare onset, but with dysfunctional regulatory marker expression compared to drug-free remission. Significant clonal expansion is observed in T cells, but not B cells, after drug cessation; this is widespread throughout memory CD8+ T cell subsets but limited to the granzyme-expressing cytotoxic subset within CD4+ memory T cells. Based on our observations, we suggest a model of immune dysregulation for understanding RA flare, with potential for further translational research towards novel avenues for its treatment and prevention.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45213-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45213-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45213-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().