Pediatric rheumatology

Identification and validation of interferon-driven gene signature as a predictor of response to methotrexate in juvenile idiopathic arthritis

Ann Rheum DisPublished Biomarker discovery and validation study

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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