Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis
Authors' conclusion
In children with JIA, a high IFN-driven gene signature is associated with a better response to MTX than those with a low IFN-driven gene signature.
Study context
- Population
- Children with non-systemic juvenile idiopathic arthritis (JIA) before starting methotrexate (MTX)
- Participants
- 97 / 26 / 47 / 240
- Comparison
- High vs low baseline interferon (IFN)-driven gene signature, against response to MTX
- Discoveryn = 97
- Validation cohort 1n = 26
- Validation cohort 2n = 47
- Adult rheumatoid arthritis (RA)n = 240
- Outcome
- Association of pre-treatment gene expression with response to MTX treatment
- Follow-up
- 6 months
Methodological detailsdiscovery cohort and 2 validation cohorts, RNA sequencing of sorted CD4+, CD8+, CD14+, CD19+ cells and peripheral blood mononuclear cells (PBMC), pre-treatment gene expression, parallel analysis in adult RA
- Discovery cohort and 2 validation cohorts
- RNA sequencing of sorted CD4+, CD8+, CD14+, CD19+ cells and PBMC
- Pre-treatment gene expression
- Parallel analysis in adult RA
Performance
As reported in the abstract
Association of baseline IFN-driven gene expression with response to MTX
- Baseline expression of genes driven by IFN alpha (type-I) or gamma (type-II) associated with response at 6 months in 3 independent JIA cohorts
- Children with higher baseline expression of IFN-stimulated genes before MTX more likely to be good responders
Further findings
Comparison with adult RA
- Differences between PBMC and whole blood gene expression associations with response
Original publication
Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis. Ann Rheum Dis. Published 20 May 2025. doi:10. 1016/ j. ard. 2025. 03. 007
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