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Updated: Sep 3, 2026
Quantitative Magnetic Resonance Imaging of Skeletal Muscle Disease
Published on: December 18, 2016
Gene expression profiling in DQA1*0501+ children with untreated dermatomyositis: a novel model of pathogenesis
Zivana Tezak1, Eric P Hoffman, Jennica L Lutz
1Research Center for Genetic Medicine, Children's National Medical Center, Washington, DC, USA.
Insights
Juvenile dermatomyositis (JDM) in children involves immune system dysregulation, potentially triggered by viral infections. Gene expression reveals an interferon signature and muscle damage similar to other myopathies.
Area of Science:
- Pediatric Rheumatology
- Immunology
- Molecular Biology
Background:
- Juvenile dermatomyositis (JDM) is the most common pediatric inflammatory myopathy, characterized by systemic vasculopathy.
- Epidemiological and immunological data suggest antigen-driven pathophysiology, possibly initiated by antecedent infections.
- Genetic susceptibility, indicated by DQA1*0501 positivity, plays a role in JDM development.
Purpose of the Study:
- To compare gene expression profiles in muscle biopsies of untreated JDM children with other conditions and controls.
- To investigate the molecular mechanisms underlying JDM pathogenesis, focusing on immune response and muscle pathology.
- To explore the potential role of viral triggers in JDM development.
Main Methods:
- Gene expression profiling of muscle biopsies from four DQA1*0501(+) JDM children.
- Comparison with gene expression data from Duchenne muscular dystrophy patients, an in vitro antiviral model (NF90), and healthy controls.
- Validation of key gene expressions using quantitative real-time PCR, immunofluorescence, and immunolocalization.
Main Results:
- Approximately 47% of dysregulated genes in JDM were linked to the immune response, particularly interferon (IFN)-alpha/beta-inducible genes.
- Elevated expression of IFN-alpha/beta-inducible genes (e.g., 6-16, p78, LMP2, TAP1) was observed, mirroring an in vitro viral resistance model.
- JDM muscle tissue exhibited gene expression patterns of myofiber necrosis and regeneration, overlapping with Duchenne muscular dystrophy.
Conclusions:
- The findings support a model where antigen (potentially viral) induction triggers autoimmune responses in genetically susceptible children.
- JDM pathogenesis involves a dynamic interplay between muscle, vascular, and immune systems, characterized by an IFN-alpha/beta signature.
- The study highlights the complex molecular landscape of JDM, suggesting a viral trigger superimposed on muscle damage pathways.
Abstract:
Juvenile dermatomyositis (JDM), the most common pediatric inflammatory myopathy, is a systemic vasculopathy affecting young children. Epidemiology studies documenting an antecedent illness in the 3 mo before the first definite symptom (rash and/or weakness) of JDM are supported by immunologic data that suggest that the disease pathophysiology is Ag driven. The purpose of this study was to compare the gene expression profiles in muscle biopsies of four untreated DQA1*0501(+) JDM children with profiles from children with a known necrotizing myopathy (Duchenne muscular dystrophy), as well as an in vitro antiviral model (NF90), and healthy pediatric controls. Nearly half (47%) of the dysregulated genes in JDM were associated with the immune response. In particular, increased expression of IFN-alphabeta-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-alphabeta transcription cascade seen in the in vitro viral resistance model. The IFN-alphabeta-inducible profile was superimposed on transcription profiles reflective of myofiber necrosis and regeneration shared with Duchenne muscular dystrophy. Expressed genes were confirmed by quantitative real-time PCR (6-16), immunofluorescence (thrombospondin 4), and immunolocalization (IFN-gamma, p21). We hypothesize that these data support a model of Ag (?viral) induction of an apparent autoimmune disease based on dynamic interaction between the muscle, vascular, and immune systems in the genetically susceptible (DQA1*0501(+)) child.
