Updates on interferon in juvenile dermatomyositis: pathogenesis and therapy

Abstract

Purpose of review 

This review provides updates regarding the role of interferon (IFN) in juvenile dermatomyositis (JDM), including comparison to interferonopathies and therapeutic implications.

Recent findings 

Transcriptomic and protein-based studies in different tissues and peripheral IFN-α assessment have demonstrated the importance of the dysregulated IFN pathway in JDM. Additional studies have validated IFN-regulated gene and protein expression correlation with disease activity in blood and muscle, with potential to predict flares. Type I and II IFN both are dysregulated in peripheral blood and muscle, with more type I IFN in skin. Muscle studies connects hypoxia to IFN production and IFN to vascular dysfunction and muscle atrophy. JDM overlaps with interferonopathy phenotype and IFN signature. There are multiple case reports and case series noting decreased IFN markers and clinical improvement in refractory JDM with Janus kinase (JAK) inhibitors.

Summary 

Studies confirm IFN, particularly type I and II IFN, is an important part of JDM pathogenesis by the level of dysregulation and correlation with disease activity, as well as IFN recapitulating key JDM muscle pathology. Smaller studies indicate there may be differences by myositis-specific autoantibody group, but validation is needed. JAK inhibitors are a promising therapy as they can inhibit IFN signaling, but further study is needed regarding which patients will benefit, dosing, and safety monitoring.