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

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 TalbotDebra Crumrine, Robert N. Cole, Peter Elias, Karsten Zengler, Max A. Seibold, Evgeny Berdyshev, Elena Goleva

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


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.

Original languageEnglish (US)
Article numbereaav2685
JournalScience translational medicine
Issue number480
StatePublished - 2019

ASJC Scopus subject areas

  • Medicine(all)


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