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
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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