Blood molecular subtypes to guide precision treatment strategies in systemic juvenile idiopathic arthritis
Authors' conclusion
Neutrophil activation was the key feature in active sJIA. The three molecular subtype scheme enables the formulation of precision medicine strategies in sJIA.
Study context
- Population
- Patients with sJIA, polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis and healthy controls (blood transcriptomic dataset)
- Participants
- 168 / 254 / 96 / 40 / 220
- Comparison
- Three molecular sJIA subgroups (C1, C2, C3); sJIA vs other JIA subtypes and healthy controls
- sJIAn = 168
- Polyarticular JIAn = 254
- Oligoarticular JIAn = 96
- Enthesitis-related arthritisn = 40
- Healthy controlsn = 220reference
- Outcome
- Molecular signatures of sJIA subgroups
Methodological detailsblood transcriptomic analysis, unsupervised clustering, gene set enrichment, network-based centrality analyses
- Blood transcriptomic analysis
- Unsupervised clustering
- Gene set enrichment
- Network-based centrality analyses
Main finding
As reported in the abstract
- Neutrophil degranulation and IL-1 signaling pathway shared key processes for the three subgroups
- Proinflammatory signals (TNF, IL-6, TLR, G-CSF signaling) varied across subgroups
- C1 most inflammatory subset, high-risk profile for macrophage activation syndrome
- C2 had the most activated IL-1 and IL-18 signaling pathways
- C2 and C3 have higher levels of interferon-stimulated signatures
Further findings
Canakinumab treatment response (canakinumab-treated dataset)
- Response correlated with IL1B expression and NF-κB signaling pathway; neutrophil activation-associated processes effectively suppressed in good responders
Candidate drugs counteracting sJIA gene expression
- GSK3B and p38 MAPK inhibitors showed a significant counteracting effect on perturbed sJIA gene expression
Original publication
Blood molecular subtypes to guide precision treatment strategies in systemic juvenile idiopathic arthritis. Arthritis Res Ther. Published 8 February 2025. doi:10.
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