Gene Expression Profiling in DQA10501 super(+) Children with Untreated Dermatomyositis: A Novel Model of Pathogenesis

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 t...

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Bibliographic Details
Published in:The Journal of immunology (1950) 2002-04, Vol.168 (8), p.4154-4163
Main Authors: Tezak, Z, Hoffman, E P, Lutz, J L, Fedczyna, TO, Stephan, D, Bremer, E G, Krasnoselska-Riz, I, Kumar, A, Pachman, L M
Format: Article
Language:English
Subjects:
a-Interferon
b-Interferon
histocompatibility antigen HLA
Juvenile dermatomyositis
vasculopathy
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Summary: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 super(+) 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- alpha beta -inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN- alpha beta transcription cascade seen in the in vitro viral resistance model. The IFN- alpha beta -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 super(+)) child.
ISSN:0022-1767