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

Wiley - Tập 56 Số 11 - Trang 3784-3792 - 2007
Ronan J. Walsh1, Sek Won Kong2,3, Yihong Yao4, Bahija Jallal4, Peter A. Kiener4, Alan H. Beggs5, Anthony A. Amato5, Steven A. Greenberg6,7,3
1Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA
2Children’s Hospital Boston and Harvard Medical School, Boston, Massachusetts
3Massachusetts Institute of Technology, Cambridge, Massachusetts
4MedImmune, Inc., Gaithersburg, Maryland
5Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts
6Brigham and Women's Hospital, Children's Hospital Boston
7Harvard Medical School, Boston, Massachusetts

Tóm tắt

AbstractObjectiveTo 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.MethodsWe 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.ResultsMost 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.ConclusionDM 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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Tài liệu tham khảo

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Wiley

Tập 56 Số 11

3784-3792

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