The interferon in idiopathic inflammatory myopathies: Different signatures and new therapeutic perspectives. A literature review
Idiopathic inflammatory myopathies (IIM), even though sharing common clinical manifestations, are characterized by diversified molecular pathogenetic mechanisms which may account for the partial inefficacy of currently used immunomodulatory drugs. In the last decades, the role of interferon (IFN) in...
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Veröffentlicht in: | Autoimmunity reviews 2023-06, Vol.22 (6), p.103334, Article 103334 |
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Sprache: | eng |
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Zusammenfassung: | Idiopathic inflammatory myopathies (IIM), even though sharing common clinical manifestations, are characterized by diversified molecular pathogenetic mechanisms which may account for the partial inefficacy of currently used immunomodulatory drugs. In the last decades, the role of interferon (IFN) in IIM has been extensively elucidated thanks to genomic and proteomic studies which have assessed the molecular signature at the level of affected tissues or in peripheral blood across distinct IIM subtypes. A predominant type I IFN response has been shown in dermatomyositis (DM), being especially enhanced in anti-melanoma differentiation-associated gene 5 (MDA5)+ DM, while a type 2 IFN profile characterizes anti-synthetase syndrome (ASyS) and inclusion body myositis (IBM); conversely, a less robust IFN footprint has been defined for immune-mediated necrotizing myopathy (IMNM). Intracellular IFN signaling is mediated by the janus kinase/signal transducer and activator of transcription (JAK/STAT) through dedicated transmembrane receptors and specific cytoplasmic molecular combinations. These results may have therapeutic implications and led to evaluating the efficacy of new targeted drugs such as the recently introduced janus kinase inhibitors (JAKi), currently approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis.
In this review we aim to summarize the most significant evidence of IFN role in IIM pathogenesis and to describe the current state of the art about the ongoing clinical trials on IFN-targeting drugs, with particular focus on JAKi.
•The IFN system plays an important role in the pathogenesis of IIM.•Different IIM disease subtypes are characterized by distinctive IFN signatures.•Molecular signatures should be exploited to implement targeted treatment strategies.•Several IFN-modulating therapies are under evaluation for the treatment of IIM.•Promising results come from the use of JAK inhibitors in IIM treatment. |
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ISSN: | 1568-9972 1568-9972 1873-0183 |
DOI: | 10.1016/j.autrev.2023.103334 |