Early-onset pediatric atopic dermatitis is characterized by Th2/Th17/Th22- centered inflammation and lipid alterations

ABSTRACT: Background: While 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 of better treatments. Objective: We sought to globally profile the skin of infants with AD compared to adults with AD and healthy controls. Methods: We performed microarray, RT-PCR and fluorescence microscopy studies in infants and young children (<5yo) with early-onset AD (<6mo) compared to age-matched controls and adults with longstanding AD. Results: Transcriptomic analyses revealed profound differences between early-onset pediatric vs. longstanding adult AD, not only in lesional but also non-lesional tissues. While both patient populations harbored Th2-centered inflammation, pediatric AD also showed significant Th17-skewing, but lacked the Th1 upregulation that characterizes adult AD. Defects in lipid barrier (e.g. ELOVL3, DGAT2) and tight junction regulation (e.g. Claudins 8 and 23) were evident in both groups but, unlike adult AD which showed the classic downregulation of epidermal differentiation and cornification products, pediatric AD exhibited relatively normal expression of these genes. Some lipid-associated mediators (such as FAR2 and FA2H) even showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H, DGAT2) showed inverse correlations with transepidermal water loss/TEWL, a functional measure of the epidermal barrier. Conclusions: Children and adult AD skin samples 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107361 | GEO | 2018/05/21

REPOSITORIES: GEO