Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum - 02/10/14
Abstract |
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-α 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.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, eczema herpeticum, herpes simplex virus, interferon regulatory factor 3, interferon regulatory factor 7, type I interferon, type III interferon
Abbreviations used : AD, ADEH+, ADEH−, FDR, HSE, HSV-1, IPA, IRF, PCA, qPCR, RNA-seq, RPKM, TLR
Plan
| This work was funded by National Institutes of Health/National Institute of Allergy and Infectious Disease Atopic Dermatitis Research Network contract HHSN272201000020C. |
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| Disclosure of potential conflict of interest: D. Y. M. Leung has received research support from the National Institutes of Health/National Institute of Allergy and Infectious Diseases (HHSN272201000020C and R01 AR41256). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 134 - N° 4
P. 848-855 - octobre 2014 Retour au numéro
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