OP0134 Increased Muscle Interferon-γ Expression Levels in Juvenile Dermatomyositis
Authors: G.M. Moneta, A. D'Amico, M. Verardo, D. Pires Marafon, L. Bracci-Laudiero, F. De Benedetti, R. Nicolai
Journal: Annals of the Rheumatic Diseases (2015)

<h3>Background</h3> 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. <h3>Objectives</h3> In this study, we focused our attention on the inflammatory cytokine interferon-γ (IFN-γ), the only member of type II class of interferons. We analysed muscle biopsy samples of JDM-affected children to characterize IFN-γ expression levels and to identify possible correlations with clinical features. <h3>Methods</h3> 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-γ, 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. <h3>Results</h3> 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, physician9s global assessment of the patient9s 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-γ, CXCL-9, CXCL-10, CXCL-11 and CIITA expression were significantly higher in JDM biopsy samples compared with those of DMD patients (<i>p</i> =0.0004, <i>p</i> =0.0004, <i>p</i> &lt;0.0001, <i>p</i> &lt;0.0001, <i>p</i> =0.0017, respectively). In JDM patients we found that IFN-γ mRNA levels significantly correlated with CXCL-9 and CIITA mRNA levels; on the contrary, we do not observed correlations between IFN-γ 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. <h3>Conclusions</h3> The increased muscle expression of IFN-γ and IFN-γ-correlated genes in muscle biopsy samples of JDM patients suggests a potential pathogenic role of IFN-γ in JDM. <h3>References</h3> Bellutti Enders F., et al.; Correlation of CXCL10, Tumor Necrosis Factor Receptor Type II, and Galectin 9 with disease activity in juvenile dermatomyositis; Arthritis &amp; Rheumatology; 2014; 66:2281-2289. Reed A.M., et al.; Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course; Arthritis &amp; Rheumatism; 2012; 64:4078-4086. <h3>Disclosure of Interest</h3> None declared