Rheumatoid arthritis

CD4+CD8αlow T Cell Clonal Expansion Dependent on Costimulation in Patients With Rheumatoid Arthritis

Arthritis RheumatolPublished Mechanistic study

Authors' conclusion

In patients with RA, clonal expansion of CD4+ T cell culminates in the emergence of peripheral CD4+CD8αlow T cells, which are associated with disease activity and diminished upon abatacept treatment and could contribute to disease pathogenesis.

Study context

Population
Patients with rheumatoid arthritis (RA), patients with PsA and healthy donors; Single-cell RNA (scRNA)/T cell receptor (TCR) sequencing in RA and healthy controlsscRNA/TCR sequencing in RA 3 · healthy controls 2
Participants
53 / 52 / 50
Comparison
RA vs PsA vs healthy donors; RA before vs after abatacept for 12 weeks
  • RAn = 53
  • PsAn = 52
  • Healthy donorsn = 50reference
Outcome
Frequency and clonality of peripheral CD4+CD8+ T cells and their subpopulations
Methodological detailssingle-cell RNA and TCR sequencing, flow cytometry, prospective abatacept cohort
  • Single-cell RNA and TCR sequencing
  • Flow cytometry
  • Prospective abatacept cohort

Main finding

As reported in the abstract

Peripheral CD4+CD8αlow T cells
  • Increase of CD4+ T cells expressing CD8α in RA vs both PsA and healthy controls
  • CD4+CD8αlow T cells are part of large T cell clones, clustering separately from CD4+CD8- T cell clones in scRNA sequencing (scRNA-seq) gene expression analysis

Further findings

Frequency of peripheral CD4+CD8αlow T cells with abatacept · 12 weeks

Abatacept significantly reduced frequency of peripheral CD4+CD8αlow T cells, linked to reduction in disease activity

Original publication

CD4+CD8αlow T Cell Clonal Expansion Dependent on Costimulation in Patients With Rheumatoid Arthritis. Arthritis Rheumatol. Published 4 September 2024. doi:10.1002/art.42960

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