Interferon-α/β-mediated innate immune mechanisms in dermatomyositis

Steven A. Greenberg, Jack L. Pinkus, Geraldine S. Pinkus, Travis Burleson, Despina Sanoudou, Rabi Tawil, Richard J. Barohn, David S. Saperstein, Hannah R. Briemberg, Maria Ericsson, Peter Park, Anthony A. Amato

Research output: Contribution to journalArticle

369 Citations (Scopus)

Abstract

Dermatomyositis has been modeled as an autoimmune disease largely mediated by the adaptive immune system, including a local Immorally mediated response with B and T helper cell muscle infiltration, antibody and complement-mediated injury of capillaries, and perifascicular atrophy of muscle fibers caused by ischemia. To further understand the pathophysiology of dermatomyositis, we used microarrays, computational methods, immunohistochemistry and electron microscopy to study muscle specimens from 67 patients, 54 with inflammatory myopathies, 14 with dermatomyositis. In dermatomyositis, genes induced by interferon-α/ β were highly overexpressed, and immunohistochemistry for the interferon-α/β inducible protein MxA showed dense staining of perifascicular, and, sometimes all myofibers in 8/14 patients and on capillaries in 13/14 patients. Of 36 patients with other inflammatory myopathies, 1 patient had faint MxA staining of myofibers and 3 of capillaries. Plasmacytoid dendritic cells, potent CD4+ cellular sources of interferon-α, are present in substantial numbers in dermatomyositis and may account for most of the cells previously identified as T helper cells. In addition to an adaptive immune response, an innate immune response characterized by plasmacytoid dendritic cell infiltration and interferon-α/β inducible gene and protein expression may be an important part of the pathogenesis of dermatomyositis, as it appears to be in systemic lupus erythematosus.

Original languageEnglish
Pages (from-to)664-678
Number of pages15
JournalAnnals of Neurology
Volume57
Issue number5
DOIs
Publication statusPublished - 1 May 2005
Externally publishedYes

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Dermatomyositis
Interferons
Myositis
Helper-Inducer T-Lymphocytes
Dendritic Cells
Immunohistochemistry
Staining and Labeling
Muscles
Muscular Atrophy
Adaptive Immunity
Innate Immunity
Systemic Lupus Erythematosus
Autoimmune Diseases
Immune System
Electron Microscopy
Proteins
Ischemia
Gene Expression
Antibodies
Wounds and Injuries

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Greenberg, S. A., Pinkus, J. L., Pinkus, G. S., Burleson, T., Sanoudou, D., Tawil, R., ... Amato, A. A. (2005). Interferon-α/β-mediated innate immune mechanisms in dermatomyositis. Annals of Neurology, 57(5), 664-678. https://doi.org/10.1002/ana.20464

Interferon-α/β-mediated innate immune mechanisms in dermatomyositis. / Greenberg, Steven A.; Pinkus, Jack L.; Pinkus, Geraldine S.; Burleson, Travis; Sanoudou, Despina; Tawil, Rabi; Barohn, Richard J.; Saperstein, David S.; Briemberg, Hannah R.; Ericsson, Maria; Park, Peter; Amato, Anthony A.

In: Annals of Neurology, Vol. 57, No. 5, 01.05.2005, p. 664-678.

Research output: Contribution to journalArticle

Greenberg, SA, Pinkus, JL, Pinkus, GS, Burleson, T, Sanoudou, D, Tawil, R, Barohn, RJ, Saperstein, DS, Briemberg, HR, Ericsson, M, Park, P & Amato, AA 2005, 'Interferon-α/β-mediated innate immune mechanisms in dermatomyositis', Annals of Neurology, vol. 57, no. 5, pp. 664-678. https://doi.org/10.1002/ana.20464
Greenberg SA, Pinkus JL, Pinkus GS, Burleson T, Sanoudou D, Tawil R et al. Interferon-α/β-mediated innate immune mechanisms in dermatomyositis. Annals of Neurology. 2005 May 1;57(5):664-678. https://doi.org/10.1002/ana.20464
Greenberg, Steven A. ; Pinkus, Jack L. ; Pinkus, Geraldine S. ; Burleson, Travis ; Sanoudou, Despina ; Tawil, Rabi ; Barohn, Richard J. ; Saperstein, David S. ; Briemberg, Hannah R. ; Ericsson, Maria ; Park, Peter ; Amato, Anthony A. / Interferon-α/β-mediated innate immune mechanisms in dermatomyositis. In: Annals of Neurology. 2005 ; Vol. 57, No. 5. pp. 664-678.
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