IFN-α levels correlate with muscle disease activity only in juvenile dermatomyositis patients with anti-MDA5+ autoantibodies.

Abstract

This study aimed to establish the role of myositis-specific antibodies (MSAs) in the association between type I interferon (IFN-I) plasma levels and disease activity in juvenile dermatomyositis (JDM). We prospectively obtained 400 samples from 101 JDM patients from two independent cohorts. Autoantibody levels were determined for all patients. Muscle activity was assessed using the Childhood-Myositis Assessment Scale (CMAS). Two characterized homebrew digital ELISAs measuring, respectively, all 12 IFN-α subtype protein and IFN-β were used to quantify IFN-I in patient plasma. Receiver operating characteristic (ROC) curve analysis was used to identify IFN-I thresholds associated with CMAS changes. Correlations between IFN-I levels and CMAS were assessed at recruitment using Spearman's test, and longitudinally using mixed-effects models to account for repeated measures. IFN-α levels were higher in melanoma differentiation-associated gene 5 (MDA5)-positive patients while IFN-β levels were comparable across MSA subgroups. IFN-β was found to be more effective than IFN-α in distinguishing between active and inactive muscle disease, and between severe and non-severe disease status. Over the disease course, we identified IFN-β as a reliable biomarker of muscle disease activity regardless of MSA expression. In contrast, IFN-α levels showed a specific association with CMAS only in MDA5-positive patients. The exclusive association of IFN-α levels with muscle clinical score in anti-MDA5-positive patients suggests a subgroup-specific pathophysiological mechanism. These findings underscore potentially distinct roles for IFN-I subtypes (IFN-α and IFN-β) as circulating biomarkers of muscle disease activity in JDM according to MSA expression.