Whole blood gene expression profiling predicts therapeutic response at six months in patients with polyarticular
Kaiyu Jiang1, Ashley D Sawle, M Barton Frank
1Columbia University Medical Center, New York, New York.
Insights
Gene expression in peripheral blood can predict treatment outcomes in children with polyarticular juvenile idiopathic arthritis (JIA). This finding suggests peripheral blood gene expression may be a valuable tool for a new prognostic test for JIA.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Juvenile idiopathic arthritis (JIA) is a complex autoimmune disease affecting children.
- Identifying reliable prognostic markers for JIA is crucial for tailoring treatment strategies.
- Current understanding of JIA pathogenesis involves intricate genetic and immune system interactions.
Purpose of the Study:
- To investigate if peripheral whole blood gene expression profiles can predict therapeutic outcomes in children with newly diagnosed polyarticular JIA.
- To explore the potential of gene expression analysis as a prognostic tool for JIA patients.
Main Methods:
- Analysis of whole blood samples from the Trial of Early Aggressive Therapy (TREAT) in JIA patients using Illumina microarrays.
- Validation of microarray findings using real-time quantitative polymerase chain reaction (RT-qPCR).
- Application of pathway analysis and support vector machine (SVM) modeling to identify predictive gene expression signatures.
Main Results:
- Gene expression profiles were similar between rheumatoid factor (RF)-positive and RF-negative JIA patients.
- Pathway analysis indicated a wide array of biological pathways affected in JIA, aligning with existing mechanistic theories.
- Predictive modeling demonstrated a strong correlation between baseline gene expression and 6-month prognosis, independent of treatment received.
Conclusions:
- Peripheral blood gene expression is significantly associated with therapeutic outcomes in polyarticular JIA.
- Gene expression analysis in peripheral blood holds promise as a basis for developing a novel prognostic test for JIA.
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.
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