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

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 ?-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.

SUBMITTER: Leung DYM

PROVIDER: S-EPMC7676854 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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

Leung Donald Y M DYM Calatroni Agustin A Zaramela Livia S LS LeBeau Petra K PK Dyjack Nathan N Brar Kanwaljit K David Gloria G Johnson Keli K Leung Susan S Ramirez-Gama Marco M Liang Bo B Rios Cydney C Montgomery Michael T MT Richers Brittany N BN Hall Clifton F CF Norquest Kathryn A KA Jung John J Bronova Irina I Kreimer Simion S Talbot C Conover CC Crumrine Debra D Cole Robert N RN Elias Peter P Zengler Karsten K Seibold Max A MA Berdyshev Evgeny E Goleva Elena E

Science translational medicine 20190201 480

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 <i>FA</i>+) have stratum corneum (SC) abnormalities that distinguish them from AD without FA (AD <i>FA</i>-) and nonatopic (NA) controls. Transepidermal water loss was found to be incre ...[more]

PMID: 30787169

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Project description:BACKGROUND:Expression profiling of skin biopsy specimens has established molecular features of the skin in patients with atopic dermatitis (AD). The invasiveness of biopsies has prevented their use in defining individual-level AD pathobiological mechanisms (endotypes) in large research studies. OBJECTIVE:We sought to determine whether minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. METHODS:We sampled nonlesional and lesional skin tape strips and biopsy specimens from white adult patients with AD (18 male and 12 female patients; age [mean ± SE], 36.3 ± 2.2 years) and healthy control subjects (9 male and 16 female subjects; age [mean ± SE], 34.8 ± 2.2 years). AmpliSeq whole-transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsy specimens, and clinical trait correlations were performed. RESULTS:Skin tape expression profiles were distinct from skin biopsy profiles and better sampled epidermal differentiation complex genes. Skin tape expression of 29 immune and epidermis-related genes (false discovery rate < 5%) separated patients with AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of patients with AD exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes, including overexpression of IL13, IL4R, CCL22, CCR4 (log2 fold change = 5.5, 2.0, 4.0, and 4.1, respectively) and at a pathway level by TH2/dendritic cell activation. Both expression and immunostaining of skin biopsy specimens indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing Fc?RI. The type 2-high endotype group exhibited more severe disease by using both the Eczema Area and Severity Index score and body surface area covered by lesions. CONCLUSION:Minimally invasive expression profiling of nonlesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.

Dataset Information

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

Publications

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

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