Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin
Early-onset pediatric atopic dermatitis is TH2 but also TH17 polarized in skin
复制标题
DOI：
10.1016/j.jaci.2016.07.013
复制
发表时间：
2016-12-01
影响因子：
14.2
通讯作者：
Guttman-Yassky, Emma
中科院分区：
文献类型：
--
作者：
Esaki, Hitokazu;Brunner, Patrick M.;Guttman-Yassky, Emma
背景：特应性皮炎（AD）影响15%至25%的儿童和4%至7%的成人。关于AD的范式转变发现是基于成人生物标志物，反映了数十年的疾病活动，尽管85%的病例开始5年。血液表型分析显示，只有T（H）2在早发性儿童AD患者的偏斜，但在早期儿童皮肤病变的变化是未知的，限制了进步的靶向therapeutic.Objective：我们试图表征早期儿童AD皮肤表型和它的差异，从儿童对照组和成人AD。研究方法：采用免疫组化和定量实时PCR技术，我们评估了19名年龄小于5岁的AD儿童在发病6个月内的活检标本，并与AD或银屑病成人以及儿童和成人对照组进行了比较。在病变皮肤儿童表现出相当或更大的表皮增生（厚度和角蛋白16）和细胞浸润（CD 3（+）、CD 11 c（+）和Fc γ RI+）。与成人相似，存在T（H）2（IL-13、IL-31和CCL 17）和T（H）22（IL-22和S100 As）轴的强烈激活和一些T（H）1偏斜（IFN-γ和CXCL 10）。儿童显示T（H）17相关细胞因子和抗菌剂（IL-17 A、IL-19、CCL 20、LL 37和肽酶抑制剂3/弹力素）、T（H）9/IL-9、IL-33和先天标记物（IL-8）的诱导显著高于成人（P <0.02）。尽管在成人AD患者中存在特征性下调，但AD儿童和健康儿童中的聚丝蛋白表达相似。儿童AD患者的非病变皮肤显示炎症（特别是IL-17 A和相关分子IL-19和LL 37）和表皮增殖（角蛋白16和S100 As）标记物水平较高（P
Background: Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T(H)2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies.Objective: We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. Methods: Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects.Results: In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3(+), CD11c(+), and Fc epsilon RI+) than adults with AD. Similar to adults, strong activation of the T(H)2 (IL-13, IL-31, and CCL17) and T(H)22 (IL-22 and S100As) axes and some T(H)1 skewing (IFN-gamma and CXCL10) were present. Children showed significantly higher induction of T(H)17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T(H)9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P