Whole blood gene expression profiling predicts therapeutic response at six months in patients with polyarticular juvenile idiopathic arthritis

Arthritis Rheumatol. 2014 May;66(5):1363-71. doi: 10.1002/art.38341.

Abstract

Objective: To determine whether gene expression profiles identified in peripheral whole blood samples could be used to determine therapeutic outcome in a cohort of children with newly diagnosed polyarticular juvenile idiopathic arthritis (JIA).

Methods: Whole blood samples from the Trial of Early Aggressive Therapy (TREAT) in JIA patients were analyzed on Illumina microarrays, and differential gene expression was compared to expression in healthy controls. Microarray results were validated by real-time quantitative polymerase chain reaction in an independent cohort of samples. Pathway analysis software was used to characterize gene expression profiles. Support vector machines were used to develop predictive models for different patient classes.

Results: Differential gene expression profiles for rheumatoid factor (RF)-positive and RF-negative patients were remarkably similar. Pathway analysis revealed a broad range of affected pathways, consistent with current mechanistic theories. Modeling showed that the prognosis at 6 months was strongly linked to gene expression at presentation, irrespective of treatment.

Conclusion: Gene expression is linked to therapeutic outcome, and gene expression in the peripheral blood may be a suitable target for a prognostic test.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Arthritis, Juvenile / diagnosis
  • Arthritis, Juvenile / drug therapy*
  • Arthritis, Juvenile / genetics*
  • Child
  • Child, Preschool
  • Cohort Studies
  • Drug Therapy, Combination
  • Etanercept
  • Female
  • Gene Expression Profiling*
  • Genetic Testing
  • Humans
  • Immunoglobulin G / therapeutic use*
  • Male
  • Methotrexate / therapeutic use*
  • Pharmacogenetics*
  • Prednisolone / therapeutic use*
  • Prognosis
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Reproducibility of Results
  • Retrospective Studies
  • Rheumatoid Factor / genetics
  • Single-Blind Method
  • Time Factors
  • Treatment Outcome

Substances

  • Immunoglobulin G
  • Receptors, Tumor Necrosis Factor
  • Rheumatoid Factor
  • Prednisolone
  • Etanercept
  • Methotrexate