人特应性皮炎合并疱疹样湿疹与 IFN-γ 反应异常有关。
Human atopic dermatitis complicated by eczema herpeticum is associated with abnormalities in IFN-γ response.
机构信息
Department of Pediatrics, National Jewish Health, Denver, CO 80206, USA.
出版信息
J Allergy Clin Immunol. 2011 Apr;127(4):965-73.e1-5. doi: 10.1016/j.jaci.2011.02.010.
BACKGROUND
The basis for increased susceptibility of patients with atopic dermatitis (AD) to develop disseminated viral skin infections such as eczema herpeticum (AD with a history of eczema herpeticum, ADEH(+)) is poorly understood.
OBJECTIVE
We sought to determine whether subjects with AD prone to disseminated viral skin infections have defects in their IFN responses.
METHODS
GeneChip profiling was used to identify differences in gene expression of PBMCs from patients with ADEH(+) compared with patients with AD without a history of eczema herpeticum (ADEH(-)) and nonatopic controls. Key differences in protein expression were verified by enzyme-linked immunosorbent spot assay and/or ELISA. Clinical relevance was further demonstrated by a mouse model of disseminated viral skin infection and genetic association analysis for genetic variants in IFNG and IFNGR1 and ADEH among 435 cases and controls.
RESULTS
We demonstrate by global gene expression analysis selective transcriptomic changes within the IFN superfamily of PBMCs from subjects with ADEH(+) reflecting low IFN-γ and IFN-γ receptor gene expression. IFN-γ protein production was also significantly lower in patients with ADEH(+) (n = 24) compared with patients with ADEH(-) (n = 20) and nonatopic controls (n = 20). IFN-γ receptor knockout mice developed disseminated viral skin infection after epicutaneous challenge with vaccinia virus. Genetic variants in IFNG and IFNGR1 single nucleotide polymorphisms (SNPs) were significantly associated with ADEH (112 cases, 166 controls) and IFN-γ production: a 2-SNP (A-G) IFNGR1 haplotype (rs10457655 and rs7749390) showed the strongest association with a reduced risk of ADEH+ (13.2% ADEH(+) vs 25.5% ADEH(-); P = .00057).
CONCLUSION
Patients with ADEH(+) have reduced IFN-γ production, and IFNG and IFNGR1 SNPs are significantly associated with ADEH(+) and may contribute to an impaired immune response to herpes simplex virus.
背景
特应性皮炎（AD）患者易发生疱疹样湿疹（AD 病史中有疱疹样湿疹，ADEH(+)）等播散性病毒皮肤感染的原因尚不清楚。
目的
我们旨在确定易发生播散性病毒皮肤感染的 AD 患者是否存在 IFN 反应缺陷。
方法
采用基因芯片技术对 ADEH(+)患者与无疱疹样湿疹病史的 AD 患者（ADEH(-)）和非特应性对照者的 PBMC 基因表达谱进行分析，以确定差异表达的基因。通过酶联免疫斑点法和/或 ELISA 对关键蛋白表达的差异进行验证。通过对 435 例病例和对照者的疱疹样湿疹、IFNG 和 IFNGR1 基因遗传变异及 IFN-γ的小鼠模型和遗传关联分析进一步证明了临床相关性。
结果
通过对 ADEH(+)患者 PBMC 中 IFN 超家族的全基因组表达分析，我们发现了选择性转录组变化，反映了 IFN-γ和 IFN-γ受体基因表达降低。与 ADEH(-)患者（n=20）和非特应性对照者（n=20）相比，ADEH(+)患者（n=24）的 IFN-γ蛋白产生也显著降低。IFN-γ受体敲除小鼠在经皮接种牛痘病毒后发生播散性病毒皮肤感染。IFNG 和 IFNGR1 单核苷酸多态性（SNP）的遗传变异与 ADEH（112 例病例，166 例对照）和 IFN-γ产生显著相关：IFNGR1 单核苷酸多态性（rs10457655 和 rs7749390）的 2-SNP（A-G）单体型与 ADEH+风险降低呈最强相关（13.2% ADEH(+)比 25.5% ADEH(-)；P=0.00057）。
结论
ADEH(+)患者 IFN-γ产生减少，IFNG 和 IFNGR1 SNP 与 ADEH(+)显著相关，可能导致对单纯疱疹病毒的免疫反应受损。
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