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


CONCLUSIONS
Gene expression is linked to therapeutic outcome, and gene expression in the peripheral blood may be a suitable target for a prognostic test.
Columbia University Medical Center, New York, New York.
Kaiyu
K
Jiang
Ashley D
AD
Sawle
M Barton
MB
Frank
Yanmin
Y
Chen
Carol A
CA
Wallace
James N
JN
Jarvis
D000293:Adolescent; D001171:Arthritis, Juvenile / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D020869:Gene Expression Profiling; D005820:Genetic Testing; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use*; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D010597:Pharmacogenetics; D011239:Prednisolone / Q000627:therapeutic use*; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012217:Rheumatoid Factor / Q000235:genetics; D016037:Single-Blind Method; D013997:Time Factors; D016896:Treatment Outcome
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D012217:Rheumatoid Factor; D011239:Prednisolone; D000068800:Etanercept; D008727:Methotrexate