IFIH1 and DDX58 gene variants in pediatric rheumatic diseases

ARTICLE HIGHLIGHTS

Research background

The IFIH1 gene and the DDX58 gene both are involved in the interferon (IFN) type I signaling pathway. Monogenic diseases with the features of systemic rheumatic diseases were described in patients with these genetic variants. Rheumatic disease patients with IFN type I hyperactivation may have these variants.

Research motivation

Patients with rheumatic diseases with unusual manifestations (clinical features of interferonopathy) or resistant to standard treatment may have molecular variants in genes, regulating IFN I type pathway.

Research objectives

To describe children with different rheumatic diseases who have variants in DDX58 or IFIH1 genes.

Research methods

Clinical exome sequencing was performed 92 patients with different rheumatic diseases, and 14 children (10 girls and 4 boys) with DDX58 or IFIH1 genes were selected. They have the following diagnosis: Systemic autoinflammatory disease (n = 6), systemic lupus erythematosus (n = 5), juvenile dermatomyositis (n = 1), systemic onset juvenile idiopathic arthritis (n = 1), mixed connective tissue disease (n = 1). Real-time polymerase chain reaction with previous reverse transcription of RNA was used for IFN-I score assessment.

Research results

All patients had elevated IFN-I scores. Variants in both genes were described in the studied population.

Research conclusions

Patients with DDX58 and IFI1 variants had hyperactivation of the IFN I signaling pathway. The RNA-based IFN-I score is a good tool to select candidates for further genetic analysis.

Research perspectives

Research perspectives are more on molecular tests in rheumatic diseases, more functional studies confirming the role of genetic variants, and an assessment of the efficacy and safety of drugs on new indications.