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The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral.

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Presentation on theme: "The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral."— Presentation transcript:

1 The signal transducer and activator of transcription 6 gene (STAT6) increases the propensity of patients with atopic dermatitis toward disseminated viral skin infections  Michael D. Howell, PhD, Peisong Gao, MD, PhD, Byung Eui Kim, MD, Leighann J. Lesley, BS, Joanne E. Streib, BA, Patricia A. Taylor, NP, Daniel J. Zaccaro, MS, Mark Boguniewicz, MD, Lisa A. Beck, MD, Jon M. Hanifin, MD, Lynda C. Schneider, MD, Tissa R. Hata, MD, Richard L. Gallo, MD, PhD, Mark H. Kaplan, PhD, Kathleen C. Barnes, PhD, Donald Y.M. Leung, MD, PhD  Journal of Allergy and Clinical Immunology  Volume 128, Issue 5, Pages (November 2011) DOI: /j.jaci Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

2 Fig 1 ADEH+ skin supports significantly greater VV replication. A, DNA was isolated from media-or VV-stimulated nonlesional skin and analyzed for VV gene expression by means of real-time RT-PCR. B, Immunofluorescent staining for A27L. C, MFI for VV expression in the basal keratinocytes of each biopsy specimen. AS, Asthmatic patients; N, healthy subjects; PS, patients with psoriasis; QAD, patients with quiescent AD. Significant differences. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

3 Fig 2 IL-4 and IL-13 modulate VV replication. VV expression in nonlesional skin from ADEH− (A; n = 17) and ADEH+ (B; n = 6) patients infected with VV after pretreatment with or without neutralizing antibodies to IL-4 and IL-13 is shown. Significant difference: ∗P < .05. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

4 Fig 3 Constitutive STAT6 expression predisposes mice to disseminated VV infection. Satellite lesions (A), mortality rate (B), VV gene expression (C), and VV protein (D) staining in wild-type (WT) and STAT-6VT mice after infection with 5 × 106 platelet-forming units of VV are shown. VV replication was visualized by staining for the surface protein A27L (red) and wheat germ agglutinin (green) to visualize the epidermis. Tg, Transgenic. Significant differences: ∗P < .05, ∗∗P < .01, and ∗∗∗P < .001. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

5 Fig 4 Analysis of STAT6 polymorphisms in white patient samples. A, STAT6 gene structure and distribution of the genotyped SNPs across the gene (22.6 kb) on chromosome 12q13 haplotype block structure of STAT6 SNPs in white healthy control subjects (n = 166) is presented. The intensity of shading represents D′ (a measure of LD) generated by using HAPLOVIEW software, with red (100) to green reflecting higher to lower D′ values. Both rs and rs were excluded in the LD plot because of their low allele frequencies. B, Haplotype results showing omnibus P values constructed across sliding windows of sizes 2 to 5 for 8 common SNPs and ADEH+. Black vertical lines represent all individual SNP tests, and colored horizontal lines represent 2, 3, 4, and 5 haplotype tests. ∗See the detailed data in Table IV. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

6 Fig 5 Association of STAT6 SNPs with IFN-γ production in HSV-stimulated PBMCs from patients with AD (n = 44) as determined by using the log10-transformed mean spot-forming units (SFC)/106 cells. A, The association was observed for SNP rs (TC [n = 7] vs CC [n = 32)], P = .008). B, The association was observed for SNP rs (CC [n = 13] vs CT [n = 18] + TT [n = 8], P = .025). N.S., Not significant. Journal of Allergy and Clinical Immunology  , DOI: ( /j.jaci ) Copyright © 2011 American Academy of Allergy, Asthma & Immunology Terms and Conditions

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