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* Research Center for Genetic Medicine, Children’s National Medical Center, Washington, DC;
Department of Molecular Biology and Biochemistry, George Washington University, Washington, DC 20910; and
Department of Pediatrics, Division of Immunology/Rheumatology, Disease Pathogenesis Core, and
Department of Neurosurgery, Neurobiology Core, Children’s Memorial Institute for Education and Research, Northwestern University Medical School, Chicago, IL 60614
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-
-inducible genes 6-16, myxovirus resistance protein p78,
latent cytosolic transcription factor, LMP2, and TAP1 was
observed. This profile is consistent with an IFN- transcription
cascade seen in the in vitro viral resistance model. The
IFN--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-
, 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.
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