Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin.
Tape strips from early-onset pediatric atopic dermatitis highlight disease abnormalities in nonlesional skin.
复制标题
早期发作的小儿特应性皮炎的胶带条突出了非静态皮肤的疾病异常。
作者：
皮肤活检促进了我们对早发性AD婴儿/幼儿特应性皮炎/AD病理机制的理解，但在儿科人群中不可行。胶带剥离是一种新兴的微创替代方法，但缺乏早期儿科AD的全球转录组学分析。我们的目的是使用胶带提供近期发作的中重度AD婴儿/幼儿的整体病变和非病变皮肤概况。从19名患有早发性中重度AD（≤6个月）的婴儿/幼儿（<5岁;病变和非病变）和17名健康对照中收集了16条胶带用于RNA测序分析。与健康皮肤相比，我们鉴定了1829个病变性AD和662个非病变性AD差异表达基因/DEG（倍数变化≥2，FDR <0.05），样品回收率为100%。皮损和非皮损皮肤均显示出Th 2（CCL 17和IL 4 R）和Th 22/Th 17（IL 36 G、CCL 20和S100 As）相关基因的显著失调，在很大程度上缺乏显著的Th 1偏斜。终末分化（FLG和FLG 2）、脂质合成/代谢（FIGVL 3和FA 2 H）和紧密连接（CLDN 8）基因的显著下调主要见于病变性AD。Th 2指标与表皮屏障基因亚群和单个基因之间存在显著的负相关性（FLG与IL-4 R和CCL 17; r <-0.4，P <0.05）。在病变性和/或非病变性AD中，临床指标（体表面积/BSA、瘙痒ADQ和经表皮水分丢失/TEWL）与免疫和屏障mRNA之间也存在显著相关性（FLG/FLG 2与TEWL; r <-0.4，P <0.05）。在早发性儿科AD中使用胶带条的RNA-seq分析捕获了病变和非病变皮肤中的免疫和屏障改变。胶带条提供深入了解疾病病理机制和皮肤疾病活动。从19名早发性（≤6个月）、中度至重度AD的婴儿/幼儿（年龄0-5岁;病变和非病变）和17名健康对照中收集胶带条用于RNA测序分析。我们确定了2491个差异表达的基因在AD与健康皮肤。我们观察到Th 2和Th 22/Th 17相关标志物的显著失调，很大程度上缺乏Th 1偏斜。屏障相关基因的显著减少主要见于病变皮肤。缩略语：AD，特应性皮炎; DEG，差异表达基因
Skin biopsies promote our understanding of atopic dermatitis/AD pathomechanisms in infants/toddlers with early-onset AD, but are not feasible in pediatric populations. Tape strips are an emerging, minimally invasive alternative, but global transcriptomic profiling in early pediatric AD is lacking. We aimed to provide global lesional and nonlesional skin profiles of infants/toddlers with recent-onset, moderate-to-severe AD using tape strips. Sixteen tape strips were collected for RNA-seq profiling from 19 infants/toddlers (<5 years old; lesional and nonlesional) with early-onset moderate-to-severe AD (≤6 months) and 17 healthy controls. We identified 1829 differentially expressed genes/DEGs in lesional AD and 662 DEGs in nonlesional AD, vs healthy skin (fold-change ≥2, FDR <0.05), with 100% sample recovery. Both lesional and nonlesional skin showed significant dysregulations of Th2 (CCL17 and IL4R) and Th22/Th17 (IL36G, CCL20, and S100As)-related genes, largely lacking significant Th1-skewing. Significant down-regulation of terminal differentiation (FLG and FLG2), lipid synthesis/metabolism (ELOVL3 and FA2H), and tight junction (CLDN8) genes were primarily seen in lesional AD. Significant negative correlations were identified between Th2 measures and epidermal barrier gene-subsets and individual genes (FLG with IL-4R and CCL17; r < −0.4, P < .05). Significant correlations were also identified between clinical measures (body surface area/BSA, pruritus ADQ, and transepidermal water loss/TEWL) with immune and barrier mRNAs in lesional and/or nonlesional AD (FLG/FLG2 with TEWL; r < −0.4, P < .05). RNA-seq profiling using tape strips in early-onset pediatric AD captures immune and barrier alterations in both lesional and nonlesional skin. Tape strips provide insight into disease pathomechanisms and cutaneous disease activity. Tape strips are collected for RNA-seq profiling from 19 infants/toddlers (ages 0–5 years; lesional and nonlesional) with early-onset (≤6 months), moderate-to-severe AD and 17 healthy controls. We identify 2491 differentially expressed genes in AD vs healthy skin. We observe significant dysregulation of Th2 and Th22/Th17-related markers, largely lacking Th1 skewing. Significant decreases in barrier-related genes are seen primarily in lesional skin. Abbreviations: AD, atopic dermatitis; DEGs, differentially expressed genes
登录
查看更多内容
影响因子：
5.9
作者：
Brunner, Patrick M.;Israel, Ariel;Guttman-Yassky, Emma
通讯作者：
Guttman-Yassky, Emma
影响因子：
1.8
作者：
Dapic, Irena;Kobetic, Renata;Jakasa, Ivone
通讯作者：
Jakasa, Ivone
影响因子：
10.3
作者：
Clausen, M. -L.;Jungersted, J. M.;Agner, T.
通讯作者：
Agner, T.
DOI：
10.1016/j.jaci.2017.10.046
发表时间：
2018-04
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Dyjack N;Goleva E;Rios C;Kim BE;Bin L;Taylor P;Bronchick C;Hall CF;Richers BN;Seibold MA;Leung DYM
通讯作者：
Leung DYM
影响因子：
10.9
作者：
Guttman-Yassky, Emma;Diaz, Aisleen;Paller, Amy S.
通讯作者：
Paller, Amy S.