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

Publication date: Available online 3 May 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Patrick M. Brunner, Ariel Israel, Ning Zhang, Alexandra Leonard, Huei-Chi Wen, Thy Huynh, Gary Tran, Sarah Lyon, Giselle Rodriguez, Supriya Immaneni, Annette Wagner, Xiuzhong Zheng, Yeriel D. Estrada, Hui Xu, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky
BackgroundAlthough 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.ObjectiveWe sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects.MethodsWe 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.ResultsTranscriptomic 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 TH2-centered inflammation, pediatric AD also showed significant TH17/TH22 skewing but lacked the TH1 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.ConclusionsSkin 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.



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