Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients
Distinct transcriptomic profiles of early-onset atopic dermatitis in blood and skin of pediatric patients
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DOI：
10.1016/j.anai.2018.11.025
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发表时间：
2019-03-01
影响因子：
5.9
通讯作者：
Guttman-Yassky, Emma
中科院分区：
文献类型：
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作者：
Brunner, Patrick M.;Israel, Ariel;Guttman-Yassky, Emma
背景：特应性皮炎(AD)主要影响幼儿，但我们对AD发病机制的理解是基于长期存在的成人AD的皮肤和血液样本。早期儿童AD的基因组活检图谱显示显著的Th2和Th17/Th22偏斜，没有典型的成人Th1上调。目的：明确早期中重度儿童AD的血型及相关生物标志物。方法：比较28例AD患儿(1.2%，假发现率[FDR]<；0.05)的血细胞芯片和逆转录聚合酶链式反应(RT-PCR)，并与皮肤DEG进行比较。结果：从基因芯片中提取嗜酸性粒细胞和Th2标志(IL5RA、IL1RL1/ST2、HRH4、CCR3、SIGLEC8、PRSS33、CLC)；IL-13/IL-4/CCL22)在早期儿童AD患者外周血中表达上调，而IFNG/Th1降低。Th1标志物与临床严重程度(EASI、瘙痒、经皮水分丢失[TEWL])呈负相关，而Th2/Th17诱导的IL-19与SCORAD呈正相关。尽管一些RT-PCR定义的免疫标志物(IL-13/CCL22)在血液中增加，就像先前报道的皮肤一样，但基于基因阵列degs的重叠很少。结论：早期中重度儿童AD血细胞的全血特征主要表现为Th2/嗜酸性粒细胞特征；然而，标志物与皮肤特征有很大差异。考虑到它们的互补性，汇集血液和皮肤的生物标记物可能会改善侧写和预测，提供关于病程、过敏共病发展和对全身药物的反应的洞察。(C)2018年美国过敏、哮喘和免疫学学院。爱思唯尔公司出版，版权所有。
Background: Atopic dermatitis (AD) predominantly affects young children, but our understanding of AD pathogenesis is based on skin and blood samples from long-standing adult AD. Genomic biopsy profiling from early pediatric AD showed significant Th2 and Th17/Th22-skewing, without the characteristic adult Th1 up-regulation. Because obtaining pediatric biopsies is difficult, blood gene expression profiling may provide a surrogate for the pediatric skin signature.Objective: To define the blood profile and associated biomarkers of early moderate-to-severe pediatric AD.Methods: We compared microarrays and reverse transcription polymerase chain reaction (RT-PCR) of blood cells from 28 AD children ( 1.2 and false discovery rate [FDR] < 0.05) were then compared with skin DEGs.Results: Eosinophil and Th2 markers (IL5RA, IL1RL1/ST2, HRH4, CCR3, SIGLEC8, PRSS33, CLC from gene arrays; IL13/IL4/CCL22 from RT-PCR) were up-regulated in early pediatric AD blood, whereas IFNG/Th1 was decreased. Th1 markers were negatively correlated with clinical severity (EASI, pruritus, transepidermal water loss [TEWL]), whereas Th2/Th17-induced interleukin (IL)-19 was positively correlated with SCORAD. Although a few RT-PCR-defined immune markers (IL-13/CCL22) were increased in blood, as previously also reported for skin, minimal overlap based on gene array DEGs was seen.Conclusion: The whole blood signature of early moderate-to-severe pediatric AD blood cells show predominantly a Th2/eosinophil profile; however, markers largely differ from the skin profile. Given their complementarity, pooling of biomarkers from blood and skin may improve profiling and predictions, providing insight regarding disease course, allergic comorbidity development, and response to systemic medications. (C) 2018 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.