#JDM BACKGROUND SKIN#

#JDM BACKGROUND SKIN#

Interferon (IFN)-regulated genes (IRG) are upregulated in the blood, muscle, and skin of patients with JDM and adult dermatomyositis (DM) and correlate with disease activity, although the exact source, mechanism, and role of IFN remain unclear and detailed assessments by MSA group are lacking. Although the etiology of JDM is presently unknown, multiple genetic and environmental factors contribute. Myositis-specific autoantibodies (MSA) define phenotypic features and prognosis within JDM, with anti-TIF1, anti-NXP2, and anti-MDA5 autoantibodies being the most common MSA groups in JDM. Juvenile dermatomyositis (JDM) is a complex autoimmune disease characterized by weakness and rashes. This may reflect both a shared IFN signature, which is driven by IFN-β and STING pathways in SAVI, as well as the shared phenotype of vasculopathy in SAVI and JDM, particularly in anti-MDA5 autoantibody-positive JDM, and indicate potential therapeutic targets for JDM. Anti-MDA5 autoantibody-positive JDM IRG-S were notably more similar to SAVI. Our findings demonstrate peripheral IRG expression in JDM overlaps with monogenic interferonopathies, particularly SAVI, and correlates with disease activity. Weakness and joint disease activity (multinomial OR 0.91 and 3.3) were the best predictors of high IRG-S. IRG-S correlated moderately with JDM disease activity measures ( r s = 0.33–0.47) and more strongly with skin activity ( r s = 0.58–0.79) in anti-TIF1 autoantibody-positive patients. Overall, the contribution of individual interferon-regulated genes (IRG) in JDM was more similar to SAVI. The IFI27 proportion was significantly higher in SAVI and CANDLE than JDM, but IFIT1 contributed more to IRG-S in JDM. Among MSA groups, anti-MDA5 autoantibody-positive patients’ IRG-S overlapped most with SAVI. JDM IRG-S overlapped more with SAVI than CANDLE by PCA.

IRG-S in JDM patients were significantly higher than in HC but lower than in CANDLE or SAVI. IRG-S were correlated with disease assessments and patient characteristics. Principal component analysis (PCA) was performed, and individual genes were evaluated for their contribution to the score. MethodsĪ peripheral 28-component IRG-S assessed by NanoString™ in 57 JDM patients subtyped by MSA was compared with IRG-S in healthy controls (HC) and CANDLE/SAVI patients. The phenotypic overlap of some clinical features of CANDLE and SAVI with JDM led to the comparison of a standardized interferon-regulated gene score (IRG-S) in JDM and myositis-specific autoantibody (MSA) JDM subgroups, with CANDLE and SAVI. The Mendelian autoinflammatory interferonopathies, Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperature (CANDLE) and STING-Associated Vasculopathy with onset in Infancy (SAVI), are caused by genetic mutations and have extremely elevated IFN signatures thought to drive pathology. Juvenile dermatomyositis (JDM) is a systemic autoimmune disease with a prominent interferon (IFN) signature, but the pathogenesis of JDM and the etiology of its IFN signature remain unknown.

Jdm background