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OP0134 Increased Muscle Interferon-γ Expression Levels in Juvenile Dermatomyositis
  1. G.M. Moneta1,
  2. A. D'Amico2,
  3. M. Verardo2,
  4. D. Pires Marafon1,
  5. L. Bracci-Laudiero1,3,
  6. F. De Benedetti1,
  7. R. Nicolai1
  1. 1Division of Rheumatology
  2. 2Unit of Neuromuscular and Neurodegenrative Disease, Department of Neuroscience, Bambino Gesù Children's Hospital
  3. 3Institute of Translational Pharmacology, CNR, Rome, Italy

Abstract

Background 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.

Objectives 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.

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-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.

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-γ, 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-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.

Conclusions 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.

References

  1. Bellutti Enders F., et al.; Correlation of CXCL10, Tumor Necrosis Factor Receptor Type II, and Galectin 9 with disease activity in juvenile dermatomyositis; Arthritis & Rheumatology; 2014; 66:2281-2289.

  2. Reed A.M., et al.; Changes in novel biomarkers of disease activity in juvenile and adult dermatomyositis are sensitive biomarkers of disease course; Arthritis & Rheumatism; 2012; 64:4078-4086.

Disclosure of Interest None declared

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