Expression of Type I and Type II Interferons Is Increased in Juvenile Dermatomyositis and Related to Clinical and Histological Features

OBJECTIVES: Our aim was to evaluate expression of type I interferon (IFN?/?)- and type II IFN (IFN?)-inducible genes in muscle biopsies of JDM patients and to correlate their expression levels with histological and clinical features. METHODS: Expression levels of IFN-inducible genes and pro-inflammatory cytokines were assessed by quantitative PCR in muscle biopsies of JDM patients (n = 39), Duchenne muscular dystrophy (DMD) patients (n = 24) and healthy controls (HCs) (n = 4). Histological and immunofluorescence studies were performed on muscle biopsy sections. For each JDM patient charts were reviewed to record clinical features at time of sampling and long-term outcomes. RESULTS: Expression levels of IFN?/?-inducible genes (type I IFN score), IFN?, IFN?-inducible genes (type II IFN score), and TNF? were significantly higher in untreated JDM patients compared to DMD patients and HCs. Both type I and type II IFN scores were correlated with typical histopathological features of JDM muscle biopsies, such as infiltration of CD3+ and CD68+ cells and perifascicular atrophy. JDM patients with high type I IFN score, high type II IFN score and high TNF? expression levels showed more severe disease activity at biopsy. JDM patients with high type II IFN score at biopsy reached clinically inactive disease significantly later than patients with low type II IFN score. CONCLUSION: The increased expression of IFN-inducible genes in muscle of JDM patients and their association with histological and clinical features further support the pathogenic role in JDM for both type I and type II IFNs. This article is protected by copyright. All rights reserved.