Rheumatoid arthritis

Diversity and Clonality of T Cell Receptor Repertoire and Antigen Specificities in Small Joints of Early Rheumatoid Arthritis

Arthritis RheumatolPublished Mechanistic study

Authors' conclusion

Minimally invasive biopsies of the RA synovium allow for single-cell TCR sequencing and phenotyping. Clonally expanded, viral-reactive T cells account for part of the diverse CD4+ T cell repertoire. TRBV20-1 bias in ACPA+ patients suggests recognition of common antigens.

Study context

Population
Patients with rheumatoid arthritis (RA) at time of diagnosis before therapeutic intervention; synovial biopsy of a small joint (US-guided) or large joint (arthroscopic)
Participants
16 patients
Comparison
Anti-citrullinated protein antibody (ACPA)+ vs ACPA− early RA
  • ACPA+n = 11
  • ACPA-n = 5
Outcome
Synovial T cell receptor repertoire, T cell phenotypes and T cell specificities
Follow-up
At diagnosis, before therapeutic intervention
Methodological detailssingle-cell paired αβ T cell receptor (TCR) sequencing, flow cytometry, TCRs from expanded CD4+ clones of 4 HLA-DRB1*04:01 patients reexpressed to study antigen specificity
  • Single-cell paired αβ TCR sequencing
  • Flow cytometry
  • TCRs from expanded CD4+ clones of 4 HLA-DRB1*04:01 patients reexpressed to study antigen specificity

Main finding

As reported in the abstract

Unique TCR sequences identified

>4,000

Clonal expansions identified

225

Original publication

Diversity and Clonality of T Cell Receptor Repertoire and Antigen Specificities in Small Joints of Early Rheumatoid Arthritis. Arthritis Rheumatol. Published 26 February 2023. doi:10.1002/art.42407

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