Gene Expression Profiling in DQA1*0501+ Children with Untreated Dermatomyositis: A Novel Model of Pathogenesis
10.4049/jimmunol.168.8.4154
Crossref journal-article
Oxford University Press (OUP)
The Journal of Immunology (286)
Abstract

AbstractJuvenile 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-αβ-inducible genes 6-16, myxovirus resistance protein p78, latent cytosolic transcription factor, LMP2, and TAP1 was observed. This profile is consistent with an IFN-αβ transcription cascade seen in the in vitro viral resistance model. The IFN-αβ-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-γ, 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.

Bibliography

Tezak, Z., Hoffman, E. P., Lutz, J. L., Fedczyna, T. O., Stephan, D., Bremer, E. G., Krasnoselska-Riz, I., Kumar, A., & Pachman, L. M. (2002). Gene Expression Profiling in DQA1*0501+ Children with Untreated Dermatomyositis: A Novel Model of Pathogenesis. The Journal of Immunology, 168(8), 4154–4163.

Authors 9
  1. Zivana Tezak (first)
  2. Eric P. Hoffman (additional)
  3. Jennica L. Lutz (additional)
  4. Tamara O. Fedczyna (additional)
  5. Dietrich Stephan (additional)
  6. Eric G. Bremer (additional)
  7. Irina Krasnoselska-Riz (additional)
  8. Ajit Kumar (additional)
  9. Lauren M. Pachman (additional)
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Dates
Type When
Created 11 years, 4 months ago (April 22, 2014, 12:10 a.m.)
Deposited 8 months ago (Jan. 2, 2025, 11:51 a.m.)
Indexed 4 days, 4 hours ago (Sept. 3, 2025, 6:11 a.m.)
Issued 23 years, 4 months ago (April 15, 2002)
Published 23 years, 4 months ago (April 15, 2002)
Published Print 23 years, 4 months ago (April 15, 2002)
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@article{Tezak_2002, title={Gene Expression Profiling in DQA1*0501+ Children with Untreated Dermatomyositis: A Novel Model of Pathogenesis}, volume={168}, ISSN={1550-6606}, url={http://dx.doi.org/10.4049/jimmunol.168.8.4154}, DOI={10.4049/jimmunol.168.8.4154}, number={8}, journal={The Journal of Immunology}, publisher={Oxford University Press (OUP)}, author={Tezak, Zivana and Hoffman, Eric P. and Lutz, Jennica L. and Fedczyna, Tamara O. and Stephan, Dietrich and Bremer, Eric G. and Krasnoselska-Riz, Irina and Kumar, Ajit and Pachman, Lauren M.}, year={2002}, month=apr, pages={4154–4163} }