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Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium

Author

Listed:
  • Garrett Dunlap

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Aaron Wagner

    (University of Rochester School of Medicine and Dentistry)

  • Nida Meednu

    (University of Rochester Medical Center)

  • Ruoqiao Wang

    (University of Rochester School of Medicine and Dentistry)

  • Fan Zhang

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital
    Department of Medicine, Brigham and Women’s Hospital
    Harvard Medical School)

  • Jabea Cyril Ekabe

    (University of Rochester Medical Center)

  • Anna Helena Jonsson

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Kevin Wei

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Saori Sakaue

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital
    Department of Medicine, Brigham and Women’s Hospital
    Harvard Medical School)

  • Aparna Nathan

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital
    Department of Medicine, Brigham and Women’s Hospital
    Harvard Medical School)

  • Vivian P. Bykerk

    (Hospital for Special Surgery
    Weill Cornell Medicine)

  • Laura T. Donlin

    (Hospital for Special Surgery
    Weill Cornell Medicine)

  • Susan M. Goodman

    (Hospital for Special Surgery
    Weill Cornell Medicine)

  • Gary S. Firestein

    (University of California, San Diego;)

  • David L. Boyle

    (University of California, San Diego;)

  • V. Michael Holers

    (University of Colorado School of Medicine)

  • Larry W. Moreland

    (University of Colorado School of Medicine
    University of Pittsburgh School of Medicine)

  • Darren Tabechian

    (University of Rochester Medical Center)

  • Costantino Pitzalis

    (Queen Mary University of London
    National Institute for Health and Care Research (NIHR)
    Humanitas University and Humanitas Research Hospital)

  • Andrew Filer

    (University of Birmingham, NIHR Birmingham Biomedical Research Center and Clinical Research Facility, University of Birmingham, Queen Elizabeth Hospital
    University of Birmingham
    University of Birmingham, Queen Elizabeth Hospital)

  • Soumya Raychaudhuri

    (Brigham and Women’s Hospital and Harvard Medical School
    Brigham and Women’s Hospital
    Department of Medicine, Brigham and Women’s Hospital
    Harvard Medical School)

  • Michael B. Brenner

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Juilee Thakar

    (University of Rochester School of Medicine and Dentistry
    University of Rochester School of Medicine and Dentistry)

  • Andrew McDavid

    (University of Rochester School of Medicine and Dentistry)

  • Deepak A. Rao

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jennifer H. Anolik

    (University of Rochester Medical Center
    University of Rochester School of Medicine and Dentistry)

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease involving antigen-specific T and B cells. Here, we perform single-cell RNA and repertoire sequencing on paired synovial tissue and blood samples from 12 seropositive RA patients. We identify clonally expanded CD4 + T cells, including CCL5+ cells and T peripheral helper (Tph) cells, which show a prominent transcriptomic signature of recent activation and effector function. CD8 + T cells show higher oligoclonality than CD4 + T cells, with the largest synovial clones enriched in GZMK+ cells. CD8 + T cells with possibly virus-reactive TCRs are distributed across transcriptomic clusters. In the B cell compartment, NR4A1+ activated B cells, and plasma cells are enriched in the synovium and demonstrate substantial clonal expansion. We identify synovial plasma cells that share BCRs with synovial ABC, memory, and activated B cells. Receptor-ligand analysis predicted IFNG and TNFRSF members as mediators of synovial Tph-B cell interactions. Together, these results reveal clonal relationships between functionally distinct lymphocyte populations that infiltrate the synovium of patients with RA.

Suggested Citation

  • Garrett Dunlap & Aaron Wagner & Nida Meednu & Ruoqiao Wang & Fan Zhang & Jabea Cyril Ekabe & Anna Helena Jonsson & Kevin Wei & Saori Sakaue & Aparna Nathan & Vivian P. Bykerk & Laura T. Donlin & Susan, 2024. "Clonal associations between lymphocyte subsets and functional states in rheumatoid arthritis synovium," Nature Communications, Nature, vol. 15(1), pages 1-21, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49186-0
    DOI: 10.1038/s41467-024-49186-0
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    References listed on IDEAS

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