Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum.
Identification of novel gene signatures in patients with atopic dermatitis complicated by eczema herpeticum.
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DOI：
10.1016/j.jaci.2014.07.018
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发表时间：
2014-10
影响因子：
14.2
通讯作者：
Leung, Donald Y. M.
中科院分区：
文献类型：
--
作者：
Bin, Lianghua;Edwards, Michael G.;Heiser, Ryan;Streib, Joanne E.;Richers, Brittany;Hall, Clifton F.;Leung, Donald Y. M.
关键词：
特应性皮炎（AD）患者的一个子集易于发生播散性单纯疱疹病毒（HSV）感染，即疱疹性湿疹（ADEH+）。缺乏识别ADEH+的生物标志物。寻找外周血单个核细胞（PBMCs）中ADEH+的新基因特征。应用RNA测序（RNA-seq）方法，使用来自ADEH+和无EH病史的AD（ADEH-）的PBMC评价总体转录变化。通过qPCR或ELISA确认候选基因。当与HSV-1刺激后的ADEH− PBMC相比时，ADEH+ PBMC的转录组发生了明显的变化：792个基因以< 0.05的错误发现率（FDR）差异表达（ANOVA），15个I型和III型干扰素（IFN）基因是ADEH+中前20个下调最多的基因。我们进一步验证，与ADEH-和正常相比，ADEH+的HSV-1刺激的PBMCs中IFN-α和IL-29 mRNA和蛋白水平显着降低。干扰途径分析（IPA）表明，I型和III型IFN的上游调节因子IRF 3和IRF 7在ADEH+中基于其靶基因的下调而被显著抑制。此外，我们发现，IRF 3和IRF 7的基因表达在HSV-1刺激的PBMC中显著降低。与ADEH−相比，ADEH+的PBMC在HSV-1暴露后具有不同的免疫应答。在ADEH+中，IRF 3和IRF 7先天免疫途径的抑制可能是增加对播散性病毒感染的易感性的重要机制。
A subset of patients with atopic dermatitis (AD) is prone to disseminated herpes simplex virus (HSV) infection, i.e. eczema herpeticum (ADEH+). Biomarkers that identify ADEH+ are lacking. To search for novel ADEH+ gene signatures in peripheral blood mononuclear cells (PBMCs). A RNA-sequencing (RNA-seq) approach was applied to evaluate global transcriptional changes using PBMCs from ADEH+ and AD without a history of EH (ADEH−). Candidate genes were confirmed by qPCR or ELISA. ADEH+ PBMCs had distinct changes to the transcriptome when compared to ADEH− PBMCs following HSV-1 stimulation: 792 genes were differentially expressed at a false discovery rate (FDR) < 0.05 (ANOVA), and 15 type I and type III interferon (IFN) genes were among the top 20 most down-regulated genes in ADEH+. We further validated that IFN-α and IL-29 mRNA and protein levels were significantly decreased in HSV-1 stimulated PBMCs from ADEH+ compared to ADEH− and normal. Ingenuity pathway analysis (IPA) demonstrated that the up-stream regulators of type I and type III IFNs, IRF3 and IRF7, was significantly inhibited in ADEH+ based on the down-regulation of their target genes. Furthermore, we found that gene expression of IRF3 and IRF7 were significantly decreased in HSV-1 stimulated PBMC from ADEH+ subjects. PBMCs from ADEH+ have a distinct immune response following HSV-1 exposure compared to ADEH−. Inhibition of the IRF3 and IRF7 innate immune pathways in ADEH+ may be important mechanism for increased susceptibility to disseminated viral infection.
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影响因子：
30.8
作者：
Dupuis, S;Jouanguy, E;Casanova, JL
通讯作者：
Casanova, JL
DOI：
10.1084/jem.189.4.663
发表时间：
1999-02-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Leib DA;Harrison TE;Laslo KM;Machalek MA;Moorman NJ;Virgin HW
通讯作者：
Virgin HW
影响因子：
3.6
作者：
Averbuch, Diana;Chapgier, Ariane;Engelhard, Dan
通讯作者：
Engelhard, Dan
影响因子：
6
作者：
Ank, Nina;Paludan, Soren R.
通讯作者：
Paludan, Soren R.
影响因子：
32.4
作者：
Pérez de Diego R;Sancho-Shimizu V;Lorenzo L;Puel A;Plancoulaine S;Picard C;Herman M;Cardon A;Durandy A;Bustamante J;Vallabhapurapu S;Bravo J;Warnatz K;Chaix Y;Cascarrigny F;Lebon P;Rozenberg F;Karin M;Tardieu M;Al-Muhsen S;Jouanguy E;Zhang SY;Abel L;Casanova JL
通讯作者：
Casanova JL