Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis
Authors' conclusion
In this large series of early, untreated RA, we show that the synovial transcriptome closely mirrors clinical disease activity and correlates with synovial inflammation. Intriguingly, lower inflammation and disease activity are associated with higher ratios of M2:M1 macrophages, particularly striking in the synovial lining layer.
Study context
- Population
- Patients with early, untreated rheumatoid arthritis (RA); synovial tissue
- Participants
- 74 samples
- Comparison
- Transcriptomic patient clusters patient clusters (PtC1) vs PtC2
- PtC1n = 52
- PtC2n = 22
Methodological detailssynovial tissue RNASeq, principal components analysis (PCA) and unsupervised clustering, multiplex immunofluorescence
- Synovial tissue RNASeq
- PCA and unsupervised clustering
- Multiplex immunofluorescence
Main finding
As reported in the abstract
- PCA on the 894 most variable genes did not divide samples into distinct groups; continuum correlated with baseline disease activity
- PtC1 had significantly higher disease activity and probability of response to MTX than PtC2
- PtC1: upregulation of immune system genes; PtC2: upregulation of lipid metabolism genes (tissue resident or M2-like macrophages)
- M2-like:M1-like macrophage ratios inversely correlated with disease activity scores; associated with lower synovial immune infiltration and thinner, M2-like macrophage-rich lining layers
Original publication
Disease activity drives transcriptomic heterogeneity in early untreated rheumatoid synovitis. Ann Rheum Dis. Published 28 July 2023. doi:10.
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