Rheumatoid arthritis

Innate immune cell subsets are enriched in synovial fluid of anti-citrullinated protein antibodies (ACPA)-negative rheumatoid arthritis and characterized by distinct type I interferon (IFN) gene signatures

Ann Rheum DisPublished Mechanistic study

Authors' conclusion

This study identifies a distinct innate cell composition and type I IFN gene response in synovial joints, but not in peripheral blood, of patients with ACPA- RA. Similar IFN levels across groups suggest the IFN signature may have been primed before the cells entered the joints.

Study context

Population
Patients with ACPA- and ACPA+ rheumatoid arthritis (RA); mononuclear cells from peripheral blood (PBMC) and synovial fluid (SFMC)n = 4 per group discovery
Comparison
ACPA- RA vs ACPA+ RA
Methodological detailssingle-cell RNA sequencing, discovery and validation cohorts, flow cytometry
  • Single-cell RNA sequencing
  • Discovery and validation cohorts
  • Flow cytometry

Main finding

As reported in the abstract

  • Several macrophage subsets and cDC2 enriched in ACPA- RA synovial fluid (SF)
  • Frequency of Tph and B cells increased in ACPA+ RA SF
  • Type I IFN-stimulated genes detected in SFMC, but not PBMC, of patients with ACPA- RA
  • Type I IFN signature also observed in synovial tissue from two patients with ACPA- RA in an independent dataset
  • IFN levels higher in SF than serum; IFN-α/β production did not differ between ACPA+ and ACPA- RA

Original publication

Innate immune cell subsets are enriched in synovial fluid of ACPA-negative rheumatoid arthritis and characterized by distinct type I IFN gene signatures. Ann Rheum Dis. Published 3 October 2025. doi:10.1016/j.ard.2025.07.029

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