Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:134

Article

Bin, Lianghua¹  Edwards, Michael G.²  Heiser, Ryan¹  Streib, Joanne E.¹  Richers, Brittany¹  Hall, Clifton F.¹  Leung, Donald Y. M.^1,3 

[1] Natl Jewish Hlth, Dept Pediat, Denver, CO USA

[2] Univ Colorado Denver, Dept Med, Div Pulm Sci & Crit Care Med, Aurora, CO USA

[3] Univ Colorado, Sch Med, Dept Pediat, Aurora, CO USA

关键词: Atopic dermatitis;    eczema herpeticum;    herpes simplex virus;    interferon regulatory factor 3;    interferon regulatory factor 7;    type I interferon;    type III interferon;   

DOI  :  10.1016/j.jaci.2014.07.018

来源: Elsevier

【 摘 要 】

Background: A subset of patients with atopic dermatitis (AD) is prone to disseminated herpes simplex virus (HSV) infection (ie, atopic dermatitis with a history of eczema herpeticum [ADEH+]). Biomarkers that identify ADEH+ are lacking. Objective: We sought to search for novel ADEH+ gene signatures in PBMCs. Methods: An RNA-sequencing approach was applied to evaluate global transcriptional changes by using PBMCs from patients with ADEH+ and patients with atopic dermatitis without a history of eczema herpeticum (ADEH-). Candidate genes were confirmed by means of quantitative PCR or ELISA. Results: PBMCs from patients with ADEH+ had distinct changes to the transcriptome when compared with those from patients with ADEH- after HSV-1 stimulation: 792 genes were differentially expressed at a false discovery rate of less than 0.05 (ANOVA), and 15 type I and type III interferon genes were among the top 20 most downregulated genes in patients with ADEH+. We further validated that IFN-alpha and IL-29 mRNA and protein levels were significantly decreased in HSV-1-stimulated PBMCs from patients with ADEH+ compared with those from patients with ADEH- and healthy subjects. Ingenuity Pathway Analysis demonstrated that the upstream regulators of type I and type III interferons, interferon regulatory factor (IRF) 3 and IRF7, were significantly inhibited in patients with ADEH+ based on the downregulation of their target genes. Furthermore, we found that gene expression of IRF3 and IRF7 was significantly decreased in HSV-1-stimulated PBMCs from patients with ADEH+. Conclusions: PBMCs from patients with ADEH+ have a distinct immune response after HSV-1 exposure compared with those from patients with ADEH-. Inhibition of the IRF3 and IRF7 innate immune pathways in patients with ADEH+ might be an important mechanism for increased susceptibility to disseminated viral infection.

【 授权许可】

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