Vaccinia virus-specific molecular signature in atopic dermatitis skin

Dmitry N. Grigoryev, Michael D. Howell, Tonya N. Watkins, Yu Chi Chen, Chris Cheadle, Mark Boguniewicz, Kathleen C. Barnes, Donald Y M Leung

Research output: Contribution to journalArticle

Abstract

Background: Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown. Objective: Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV. Methods: Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline. Results: Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity. Conclusion: This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.

Original languageEnglish (US)
JournalThe Journal of Allergy and Clinical Immunology
Volume125
Issue number1-3
DOIs
StatePublished - Jan 2010

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Vaccinia virus
Atopic Dermatitis
Kaposi Varicelliform Eruption
Skin
Psoriasis
Innate Immunity
Genes
Orosomucoid
Healthy Volunteers
Complement C9
Leukotriene B4 Receptors
Thrombin Receptors
Gene Ontology
Toll-Like Receptor 4
Prothrombin
Gene Expression Profiling
Virus Diseases
Real-Time Polymerase Chain Reaction
Down-Regulation

Keywords

  • atopic dermatitis
  • Eczema vaccinatum
  • genomics
  • vaccinia virus

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Grigoryev, D. N., Howell, M. D., Watkins, T. N., Chen, Y. C., Cheadle, C., Boguniewicz, M., ... Leung, D. Y. M. (2010). Vaccinia virus-specific molecular signature in atopic dermatitis skin. The Journal of Allergy and Clinical Immunology, 125(1-3). https://doi.org/10.1016/j.jaci.2009.10.024

Vaccinia virus-specific molecular signature in atopic dermatitis skin. / Grigoryev, Dmitry N.; Howell, Michael D.; Watkins, Tonya N.; Chen, Yu Chi; Cheadle, Chris; Boguniewicz, Mark; Barnes, Kathleen C.; Leung, Donald Y M.

In: The Journal of Allergy and Clinical Immunology, Vol. 125, No. 1-3, 01.2010.

Research output: Contribution to journalArticle

Grigoryev, DN, Howell, MD, Watkins, TN, Chen, YC, Cheadle, C, Boguniewicz, M, Barnes, KC & Leung, DYM 2010, 'Vaccinia virus-specific molecular signature in atopic dermatitis skin', The Journal of Allergy and Clinical Immunology, vol. 125, no. 1-3. https://doi.org/10.1016/j.jaci.2009.10.024
Grigoryev, Dmitry N. ; Howell, Michael D. ; Watkins, Tonya N. ; Chen, Yu Chi ; Cheadle, Chris ; Boguniewicz, Mark ; Barnes, Kathleen C. ; Leung, Donald Y M. / Vaccinia virus-specific molecular signature in atopic dermatitis skin. In: The Journal of Allergy and Clinical Immunology. 2010 ; Vol. 125, No. 1-3.
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abstract = "Background: Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown. Objective: Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV. Methods: Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline. Results: Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity. Conclusion: This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.",
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AU - Barnes, Kathleen C.

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N2 - Background: Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown. Objective: Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV. Methods: Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline. Results: Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity. Conclusion: This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.

AB - Background: Eczema vaccinatum (EV), a disseminated viral skin infection, is a life-threatening complication of vaccinia virus (VV) inoculation in patients with atopic dermatitis (AD) and is thought to be associated with a defective innate immune response. However, the precise mechanism or mechanisms and key factor or factors of EV are unknown. Objective: Given that patients with psoriasis, another inflammatory skin disorder, are not susceptible to EV, we compared the global transcriptional response of skin to VV in healthy subjects, patients with psoriasis, and patients with AD, focusing on AD-specific genes. We hypothesized that differences in the transcriptional response to VV between patients with AD and patients with psoriasis or healthy subjects would identify a defective pathway or pathways that might be associated with the development of EV. Methods: Gene expression profiling of sham-treated and VV-treated unaffected skin explants from patients with AD (n = 12), patients with psoriasis (n = 12), or healthy subjects (n = 13) were generated with U133_Plus2 (54,613 probe sets) GeneChips and analyzed with the GCOS_1.4/SAM_2.1/MAPPFinder_2.0 pipeline. Results: Sixty-seven genes were significantly affected by VV in AD skin but not in psoriatic and healthy skin. Genes associated with defense response, response to wounding, and immune response were the most affected by VV in AD skin. All genes in these ontologies were downregulated, including the innate immunity genes leukotriene B4 receptor (LTB4R), orosomucoid 1 (ORM1), coagulation factor II (thrombin) receptor (F2R), complement component 9 (C9), and LPS-binding protein (LBP). These findings were confirmed by means of real-time PCR and validated by means of PubMatrix analysis. ORM1, Toll-like receptor 4 (TLR4), and NLR family pyrin domain containing 1 (NLRP1) genes were also linked to AD severity. Conclusion: This study identified groups of innate immunity genes that are associated with the aberrant response of AD skin to VV and represent potential targets for EV pathogenesis.

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