Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells

R. A. Mathias, A. Weinberg, M. Boguniewicz, D. J. Zaccaro, B. Armstrong, L. C. Schneider, T. R. Hata, Jon Hanifin, L. A. Beck, K. C. Barnes, D. Y M Leung

Research output: Contribution to journalArticle

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Abstract

Background The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. Objectives The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. Materials and methods In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). Results We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). Conclusions These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype. What's already known about this topic? Interferon (IFN)-γ-producing cells are known to be important cytotoxic effectors of immune protection against viruses. There have been limited reports of human leucocyte antigen (HLA) associations with risk of atopic dermatitis (AD), but there have been no reports of associations with risk of AD with eczema herpeticum (ADEH+). What does this study add? This study presents evidence that low IFN-γ expression in the CD8+ T-cell subset is associated with increased susceptibility of a subset of patients with AD to develop severe viral infections. The association of B7 alleles with EH in AD is significant because HLA B7 is more efficiently induced by IFN-γ than are HLA A locus products.

Original languageEnglish (US)
Pages (from-to)700-703
Number of pages4
JournalBritish Journal of Dermatology
Volume169
Issue number3
DOIs
StatePublished - Sep 2013

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Kaposi Varicelliform Eruption
Atopic Dermatitis
HLA Antigens
Interferons
Virus Diseases
T-Lymphocytes
Simplexvirus
Alleles
Phenotype
Antigen Presentation
T-Lymphocyte Subsets
Cellular Immunity
Monocytes
Blood Cells
Odds Ratio
Cytokines
Viruses
Skin
Therapeutics

ASJC Scopus subject areas

  • Dermatology

Cite this

Mathias, R. A., Weinberg, A., Boguniewicz, M., Zaccaro, D. J., Armstrong, B., Schneider, L. C., ... Leung, D. Y. M. (2013). Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells. British Journal of Dermatology, 169(3), 700-703. https://doi.org/10.1111/bjd.12382

Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells. / Mathias, R. A.; Weinberg, A.; Boguniewicz, M.; Zaccaro, D. J.; Armstrong, B.; Schneider, L. C.; Hata, T. R.; Hanifin, Jon; Beck, L. A.; Barnes, K. C.; Leung, D. Y M.

In: British Journal of Dermatology, Vol. 169, No. 3, 09.2013, p. 700-703.

Research output: Contribution to journalArticle

Mathias, RA, Weinberg, A, Boguniewicz, M, Zaccaro, DJ, Armstrong, B, Schneider, LC, Hata, TR, Hanifin, J, Beck, LA, Barnes, KC & Leung, DYM 2013, 'Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells', British Journal of Dermatology, vol. 169, no. 3, pp. 700-703. https://doi.org/10.1111/bjd.12382
Mathias, R. A. ; Weinberg, A. ; Boguniewicz, M. ; Zaccaro, D. J. ; Armstrong, B. ; Schneider, L. C. ; Hata, T. R. ; Hanifin, Jon ; Beck, L. A. ; Barnes, K. C. ; Leung, D. Y M. / Atopic dermatitis complicated by eczema herpeticum is associated with HLA B7 and reduced interferon-γ-producing CD8+ T cells. In: British Journal of Dermatology. 2013 ; Vol. 169, No. 3. pp. 700-703.
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abstract = "Background The increased susceptibility of patients with atopic dermatitis (AD) to disseminated viral skin infections such as eczema herpeticum (ADEH+) is poorly understood. Objectives The primary goal of the current study was to determine whether ADEH+ subjects have identifiable defects in cell-mediated immunity that reduce their ability to control viral infections. Materials and methods In this study, we evaluated cytokine expression by various subsets of peripheral blood mononuclear cells from ADEH+ (n = 24) compared with AD without a history of viral infections (ADEH-) (n = 20) before and after treatment with herpes simplex virus (HSV). Results We found that interferon (IFN)-γ expression after HSV treatment was lower in the CD8+ T cells and monocytes from patients with ADEH+ compared with patients who are ADEH- or nonatopic. Given the induction of CD8+ T cells as the result of antigen presentation by human leucocyte antigen (HLA) class I, consistent with the findings described above we also found that the HLA B7 allele was significantly associated with risk of the ADEH+ phenotype (odds ratio = 1·91, P = 0·02, 125 ADEH+ and 161 ADEH- subjects). Conclusions These data suggest that defects in viral-induced IFN-γ from CD8+ T cells contribute to the ADEH+ phenotype. What's already known about this topic? Interferon (IFN)-γ-producing cells are known to be important cytotoxic effectors of immune protection against viruses. There have been limited reports of human leucocyte antigen (HLA) associations with risk of atopic dermatitis (AD), but there have been no reports of associations with risk of AD with eczema herpeticum (ADEH+). What does this study add? This study presents evidence that low IFN-γ expression in the CD8+ T-cell subset is associated with increased susceptibility of a subset of patients with AD to develop severe viral infections. The association of B7 alleles with EH in AD is significant because HLA B7 is more efficiently induced by IFN-γ than are HLA A locus products.",
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AU - Zaccaro, D. J.

AU - Armstrong, B.

AU - Schneider, L. C.

AU - Hata, T. R.

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