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-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.

Conclusion: 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.