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Sci Transl Med. 2019 Feb 20;11(480). pii: eaav2685. doi: 10.1126/scitranslmed.aav2685.

The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype.

Author information

1
National Jewish Health, Denver, CO 80206, USA. leungd@njhealth.org.
2
Rho Federal Systems Division Inc., Chapel Hill, NC 27517, USA.
3
University of California, San Diego, La Jolla, CA 92093, USA.
4
National Jewish Health, Denver, CO 80206, USA.
5
Johns Hopkins University, Baltimore, MD 21218, USA.
6
University of California, San Francisco, San Francisco, CA 94121, USA.

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 FA+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD FA-) and nonatopic (NA) controls. Transepidermal water loss was found to be increased in AD FA+. Filaggrin and the proportion of ω-hydroxy fatty acid sphingosine ceramide content in nonlesional skin of children with AD FA+ were substantially lower than in AD FA- 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 FA+ had increased abundance of Staphylococcus aureus compared to NA. Increased expression of keratins 5, 14, and 16 indicative of hyperproliferative keratinocytes was observed in the SC of AD FA+. The skin transcriptome of AD FA+ 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 FA+, whereas filaggrin breakdown products were negatively correlated with AD FA+. These data suggest that the most superficial compartment of nonlesional skin in AD FA+ has unique properties associated with an immature skin barrier and type 2 immune activation.

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