Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:141

Article

Brunner, Patrick M.¹  Israel, Ariel²  Zhang, Ning^3,4  Leonard, Alexandra^3,4  Wen, Huei-Chi^3,4  Thy Huynh^5,6  Tran, Gary^5,6  Lyon, Sarah^5,6  Rodriguez, Giselle^5,6  Immaneni, Supriya^5,6  Wagner, Annette^5,6  Zheng, Xiuzhong¹  Estrada, Yeriel D.^3,4  Xu, Hui^3,4  Krueger, James G.¹  Paller, Amy S.^5,6  Guttman-Yassky, Emma^1,3,4 

[1] Rockefeller Univ, Lab Investigat Dermatol, 1230 York Ave, New York, NY 10021 USA

[2] Clalit Hlth Serv, Dept Family Med, Jerusalem, Israel

[3] Icahn Sch Med Mt Sinai, Dept Dermatol, New York, NY 10029 USA

[4] Icahn Sch Med Mt Sinai, Lab Inflammatory Skin Dis, New York, NY 10029 USA

[5] Northwestern Univ, Feinberg Sch Med, Dept Dermatol, Chicago, IL 60611 USA

[6] Northwestern Univ, Feinberg Sch Med, Dept Pediat, Chicago, IL 60611 USA

关键词: Atopic dermatitis;    pediatric;    infant;    skin barrier;    skin inflammation;   

DOI  :  10.1016/j.jaci.2018.02.040

来源: Elsevier

【 摘 要 】

Background: Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments. Objective: We sought to globally profile the skin of infants with AD compared with that of adults withAD and healthy control subjects. Methods: We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (< 5 years old) with early-onset AD (< 6 months disease duration) compared with age-matched control subjects and adults with longstanding AD. Results: Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored T(H)2-centered inflammation, pediatric AD also showed significant T(H)17/T(H)22 skewing but lacked the T(H)1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier. Conclusions: Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.

【 授权许可】

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