The Nonlesional Skin Surface Distinguishes Atopic Dermatitis with Food Allergy As a Unique Endotype

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2019 Feb 22

PMID 30787169

Citations 84

Authors

Donald Y M Leung

Agustin Calatroni

Livia S Zaramela

Petra K LeBeau

Nathan Dyjack

Kanwaljit Brar

Gloria David

Keli Johnson

Susan Leung

Marco Ramirez-Gama

Bo Liang

Cydney Rios

Michael T Montgomery

Brittany N Richers

Clifton F Hall

Kathryn A Norquest

John Jung

Irina Bronova

Simion Kreimer

C Conover Talbot Jr

Debra Crumrine

Robert N Cole

Peter Elias

Karsten Zengler

Max A Seibold

Evgeny Berdyshev

Elena Goleva

Affiliations

Soon will be listed here.

Abstract

Skin barrier dysfunction has been reported in both atopic dermatitis (AD) and food allergy (FA). However, only one-third of patients with AD have FA. The purpose of this study was to use a minimally invasive skin tape strip sampling method and a multiomics approach to determine whether children with AD and FA (AD +) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD -) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD +. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD + were substantially lower than in AD - and NA skin. These abnormalities correlated with morphologic changes in epidermal lamellar bilayer architecture responsible for barrier homeostasis. Shotgun metagenomic studies revealed that the nonlesional skin of AD + had increased abundance of compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD +. The skin transcriptome of AD + had increased gene expression for dendritic cells and type 2 immune pathways. A network analysis revealed keratins 5, 14, and 16 were positively correlated with AD +, whereas filaggrin breakdown products were negatively correlated with AD +. These data suggest that the most superficial compartment of nonlesional skin in AD + has unique properties associated with an immature skin barrier and type 2 immune activation.

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