The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype.

The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype.
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DOI:
10.1126/scitranslmed.aav2685
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发表时间:
2019-02-20
影响因子:
17.1
通讯作者:
Goleva E
Goleva E
中科院分区:
医学1区
文献类型:
--
作者:
Leung DYM;Calatroni A;Zaramela LS;LeBeau PK;Dyjack N;Brar K;David G;Johnson K;Leung S;Ramirez-Gama M;Liang B;Rios C;Montgomery MT;Richers BN;Hall CF;Norquest KA;Jung J;Bronova I;Kreimer S;Talbot CC Jr;Crumrine D;Cole RN;Elias P;Zengler K;Seibold MA;Berdyshev E;Goleva E

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皮肤屏障功能障碍在特应性皮炎(AD)和食物过敏(FA)中都有报道。然而,只有三分之一的AD患者患有FA。本研究的目的是使用微创皮肤胶带取样方法和多组学方法来确定患有AD和FA的儿童(AD FA+)是否有角质层(SC)异常,以区分他们与没有FA的AD (AD FA−)和非特应性(NA)对照。AD FA+组经皮失水增加。AD FA+患儿非病变皮肤中聚丝蛋白和ω-羟基脂肪酸鞘氨醇神经酰胺含量比例明显低于AD FA -和NA皮肤。这些异常与负责屏障内稳态的表皮板层双层结构的形态学改变有关。霰弹枪宏基因组研究显示,与NA相比,AD FA+的非病变皮肤中金黄色葡萄球菌的丰度增加。在AD FA+的SC中观察到角蛋白5、14和16的表达增加,表明角蛋白细胞增殖过度。AD FA+的皮肤转录组增加了树突状细胞和2型免疫途径的基因表达。网络分析显示角蛋白5、14和16与AD FA+呈正相关,而聚丝蛋白分解产物与AD FA+呈负相关。这些数据表明,AD FA+患者非病变皮肤的最浅层隔室具有与未成熟皮肤屏障和2型免疫激活相关的独特特性。
Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD FA+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA−) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA+ were substantially lower than in AD FA− and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD FA+ had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA+. The skin transcriptome of AD FA+ had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD FA+, whereas filaggrin breakdown products were negatively correlated with AD FA+. These data suggest that the most superficial compartment of nonlesional skin in AD FA+ has unique properties associated with an immature skin barrier and type 2 immune activation.
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