Interferons in myositis: Pathogenesis and therapy

Abstract

Idiopathic inflammatory myopathies (IIMs), or myositis, are a heterogeneous group of autoimmune diseases affecting skeletal muscle and other organs. Recent research has revealed the important role of interferons (IFNs) in the pathogenesis of IIMs. This review summarizes the three types of IFNs and their functions in the immune system, focusing on their association with different IIM subtypes. Dermatomyositis (DM) is strongly associated with Type I IFNs. In contrast, inclusion body myositis (IBM), polymyositis with mitochondrial pathology (PM-mito), and anti-synthetase syndrome (ASyS) are predominantly associated with Type II IFN. This review explores the molecular mechanisms underlying these associations and their impact on muscle function. In addition, the potential of the IFN signaling pathway as a therapeutic target for IIMs will be discussed. Several clinical trials are currently underway or planned that target the IFN pathway using JAK inhibitors and monoclonal antibodies against Type I IFNs. JAK inhibitors have shown promise in treating DM, particularly in refractory cases. However, more research is needed to fully understand their efficacy and safety profiles in IIMs. The review concludes by highlighting the importance of ongoing research in this area and the potential for new targeted therapies in treating IIMs.