Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance
Authors' conclusion
An increase in pre-DC in peripheral blood predicted RA treatment resistance.
Study context
- Population
- Patients with rheumatoid arthritis (RA) requiring addition of new treatment and healthy controls
- Participants
- 55 vs 39
- Comparison
- RA patients requiring new treatment vs healthy controls; treatment-resistant vs responsive patients
- RAn = 55
- Healthy controlsn = 39reference
- Outcome
- Association between immune cell gene modules and treatment resistance
Methodological detailsRNA sequencing of 18 peripheral blood immune cell subsets, validation by quantitative PCR (qPCR) and mass cytometry in independent cohorts, synovial single cell RNA-sequencing
- RNA sequencing of 18 peripheral blood immune cell subsets
- Validation by qPCR and mass cytometry in independent cohorts
- Synovial single cell RNA-sequencing
Main finding
As reported in the abstract
- Plasmacytoid dendritic cells (pDC) gene module reflecting expansion of pre-DC showed strongest association with treatment resistance
- Pre-DC associated gene expression and proportion of pre-DC significantly higher before treatment in treatment-resistant patients (qPCR and mass cytometry, independent cohorts)
- Type I interferon signalling negatively correlated to pre-DC gene expression
Further findings
Transcriptome changes in RA
- Enhanced interferon and IL6-JAK-STAT3 signalling in RA immune cells, partially normalised after treatment
Synovial DCs
- A cluster of synovial DCs showed features of both pre-DC and pro-inflammatory conventional DC2s
Original publication
Immunomics analysis of rheumatoid arthritis identified precursor dendritic cells as a key cell subset of treatment resistance. Ann Rheum Dis. Published 14 March 2023. doi:10.
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