Type I interferon activation in classical monocytes and GZMK+ CD8+ T cells characterises the ultrasound-negative phase of imminent rheumatoid arthritis
Authors' conclusion
In ACPA+ high-risk individuals, IFN-I-driven activation of peripheral innate CD14+ classical monocytes and GZMK+ CD8+ T cell subsets occur before the onset of subclinical synovitis when RA is imminent. Distinct inflammatory and effector programmes, including GZMB+ CD8+ T cells clonal expansion, are associated with the onset of subclinical synovitis.
Study context
- Population
- Anticitrullinated protein antibodies-positive (ACPA+) at-risk individuals who imminently progress to rheumatoid arthritis (RA), stratified by ultrasound-detectable subclinical synovitis, compared with ACPA+ nonprogressorsACPA+ imminent progressors 22 · ACPA+ nonprogressors 18
- Participants
- 11 / 11 / 18
- Comparison
- ACPA+ imminent progressors with and without ultrasound (US)-detectable subclinical synovitis, compared with ACPA+ nonprogressors
- US-negative (USneg) imminent progressorsn = 11
- US-positive (USpos) progressorsn = 11
- ACPA+ nonprogressorsn = 18
- Outcome
- Type I interferon (IFN-I) upregulation in peripheral CD14+ classical monocyte and GZMK+ CD8+ T cells
Main finding
As reported in the abstract
- IFN-I upregulation found in US-negative (USneg) imminent progressors
Further findings
CD14+ classical monocyte phenotype and CD8+ T cell clonality
- USpos progressors exhibited a phenotypic shift in CD14+ classical monocytes towards IL1ß+ expression and clonal expansion of GZMB+ cytotoxic CD8+ T cells
Clonotypic overlap of GZMB+ and GZMK+ CD8+ T cells
- GZMB+ and GZMK+ CD8+ T cells were largely clonotypically distinct
Plasma proteomics
- Shift from Toll-like receptor-associated innate pathways in USneg progressors towards effector and tissue-remodelling signatures in USpos progressors
Original publication
Type I interferon activation in classical monocytes and GZMK+ CD8+ T cells characterises the ultrasound-negative phase of imminent rheumatoid arthritis. Ann Rheum Dis. Published 22 October 2026. doi:10.
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