Type I interferon–inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis

Authors

  • Ronan J. Walsh,

    1. Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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    • Drs. Walsh and Kong contributed equally to this work.

  • Sek Won Kong,

    1. Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
    2. Massachusetts Institute of Technology, Cambridge, Massachusetts
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    • Drs. Walsh and Kong contributed equally to this work.

  • Yihong Yao,

    1. MedImmune, Inc., Gaithersburg, Maryland
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    • Drs. Yao, Jallal, and Kiener own stock or stock options in MedImmune. Dr. Amato has received consulting fees (less than $10,000) from MedImmune. Dr. Greenberg has received consulting fees and speaking fees (less than $10,000) from MedImmune.

  • Bahija Jallal,

    1. MedImmune, Inc., Gaithersburg, Maryland
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    • Drs. Yao, Jallal, and Kiener own stock or stock options in MedImmune. Dr. Amato has received consulting fees (less than $10,000) from MedImmune. Dr. Greenberg has received consulting fees and speaking fees (less than $10,000) from MedImmune.

  • Peter A. Kiener,

    1. MedImmune, Inc., Gaithersburg, Maryland
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    • Drs. Yao, Jallal, and Kiener own stock or stock options in MedImmune. Dr. Amato has received consulting fees (less than $10,000) from MedImmune. Dr. Greenberg has received consulting fees and speaking fees (less than $10,000) from MedImmune.

  • Jack L. Pinkus,

    1. Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Alan H. Beggs,

    1. Children's Hospital Boston and Harvard Medical School, Boston, Massachusetts
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  • Anthony A. Amato,

    1. Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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    • Drs. Yao, Jallal, and Kiener own stock or stock options in MedImmune. Dr. Amato has received consulting fees (less than $10,000) from MedImmune. Dr. Greenberg has received consulting fees and speaking fees (less than $10,000) from MedImmune.

  • Steven A. Greenberg

    Corresponding author
    1. Brigham and Women's Hospital, Children's Hospital Boston
    2. Harvard Medical School, Boston, Massachusetts
    3. Massachusetts Institute of Technology, Cambridge, Massachusetts
    • Division of Neuromuscular Disease, Department of Neurology, Brigham and Women's Hospital, 75 Francis Street, Boston, MA 02115
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    • Drs. Yao, Jallal, and Kiener own stock or stock options in MedImmune. Dr. Amato has received consulting fees (less than $10,000) from MedImmune. Dr. Greenberg has received consulting fees and speaking fees (less than $10,000) from MedImmune.


Abstract

Objective

To apply gene expression profiling to the study of peripheral blood mononuclear cells from patients with inflammatory myopathies, in order to provide insight into disease pathogenesis and identify potential biomarkers associated with disease activity.

Methods

We used Affymetrix whole-genome microarrays to measure the expression of ∼38,500 genes in 65 blood and 15 muscle samples from 44 patients with dermatomyositis (DM), polymyositis (PM), inclusion body myositis (IBM), myasthenia gravis, or genetically determined myopathies and from 12 healthy volunteers. In 9 patients, 2 samples were obtained at different time points, when disease was either active or improving, and these paired blood samples were also compared. Bioinformatics techniques were used to identify genes with significant differential expression among diagnostic categories and in relation to disease activity. We corroborated the microarray data with quantitative real-time reverse transcriptase–polymerase chain reaction.

Results

Most patients with active DM or PM, but not patients with IBM, had significant and high up-regulation of the type I interferon-α/β (IFNα/β)–inducible genes in blood. Furthermore, the up-regulation of these genes correlated with disease activity in DM and PM, with down-regulation occurring when disease was controlled with treatment.

Conclusion

DM and PM are diseases characterized by the systemic overexpression of IFNα/β-inducible genes. The magnitude of the overexpression of these genes is higher in DM and correlates with disease activity in both disorders. Although PM and IBM have been modeled as having similar immunologic processes occurring within muscle, there are substantial differences in the expression of IFNα/β-inducible genes in blood in these diseases.

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