Type 1 Interferon-Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite...

Area of Science:

• Immunology
• Rheumatology
• Genetics

Background:

• Rheumatic diseases involve immune system overactivation.
• Type 1 interferon (IFN) pathways are implicated in these conditions.
• Assessing disease activity often requires complex biomarkers.

Purpose of the Study:

• To investigate the correlation between whole blood type 1 IFN-stimulated gene (ISG), IL18, and CXCL9 expression and clinical disease activity in pediatric rheumatic diseases.
• To determine the optimal number of ISGs for a composite type 1 IFN score.

Main Methods:

• Collected RNA and clinical data from 171 pediatric patients with various rheumatic diseases and 38 controls.
• Assessed expression of six ISGs, IL18, and CXCL9 using real-time PCR.
• Performed correlation and threshold analyses on individual and composite gene expression data.

Main Results:

• ISG expression strongly correlated with disease activity in connective tissue diseases (CTDs), particularly juvenile dermatomyositis (JDM) and interferonopathies (IFNPs).
• Correlation was modest in systemic autoinflammatory diseases (SAIDs).
• Individual ISGs or small sets showed comparable correlation to a six-ISG composite score, simplifying analysis.

Conclusions:

• Individual ISG expression robustly reflects clinical disease activity in CTDs and IFNPs, especially JDM.
• Simplified ISG analyses are cost-effective for clinical routine.
• Varying threshold levels suggest diverse type 1 IFN overactivation mechanisms across diseases.