Increased Muscle Interferon-Gamma Expression Levels in Juvenile Dermatomyositis

Background/Purpose : Juvenile dermatomyositis (JDM) is a rare autoimmune disorder characterized by muscle weakness, skin rashes and other systemic features. The immunopathogenesis of JDM is unknown, but recent biomarker studies revealed that up-regulation of several type I interferon (IFN)-related mediators might play a role in the development of JDM. In this study, we focused our attention on the inflammatory cytokine interferon-? (IFN-?), the only member of type II class of interferons. We analysed muscle biopsy samples of JDM-affected children to characterize IFN-? expression levels and to identify possible correlations with clinical features. Methods : We identified a retrospective cohort of patients diagnosed with JDM at our Center between 2001 and 2014 and for whom a muscle biopsy was performed during diagnostic work-up. Expression levels of IFN-?, chemokine (C-X-C motif) ligand 9 (CXCL-9), chemokine (C-X-C motif) ligand 10 (CXCL-10), chemokine (C-X-C motif) ligand 11 (CXCL-11), class II major histocompatibility complex, transactivator (CIITA) were analysed by real-time PCR on muscle biopsy samples from patients with JMD (n = 18) and compared with samples from Duchenne muscular dystrophy (DMD) patients (n = 29) by Mann Withney test. Results : Median age at diagnosis of JDM patients was 5.4 years (interquartile range, IQR: 4.2-9.1), with a median disease duration at diagnosis of 2.1 months (IQR: 1.2-6.9). For each patient we recorded clinical features at diagnosis, physician's global assessment of the patient's overall disease activity on a 100-mm visual analog scale (VAS), serum levels of muscle enzymes (CK, ALT, AST, LDH), erythrocyte sedimentation rate, C-reactive protein level, and antinuclear antibodies status. Six patients were already treated with systemic glucocorticoids before time of biopsy sampling, whereas all DMD patients were untreated. Levels of IFN-?, CXCL-9, CXCL-10, CXCL-11 and CIITA expression were significantly higher in JDM biopsy samples compared with those of DMD patients (p = 0.0004, p = 0.0004, p <0.0001, p < 0.0001, p = 0.0017, respectively). In JDM patients we found that IFN- ? mRNA levels significantly correlated with CXCL-9 and CIITA mRNA levels; on the contrary, we do not observed correlations between IFN-? mRNA levels and clinical scores. JDM patients treated before biopsy were excluded from final statistics since the molecular analysis resulted strongly influenced by glucocorticoid therapy. Conclusion: The increased muscle expression of IFN-? and IFN-? correlated genes in muscle biopsy samples of JDM patients suggests a potential pathogenic role of IFN-? in JDM.