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

Abstract

Patients with atopic dermatitis and food allergy have an immature epithelial barrier and type 2 immune activation in their skin. Digging skin deep Disrupted epithelial barriers are thought to be central to development of allergic disorders such as atopic dermatitis, which is commonly associated with food allergy. Leung et al. performed repeated skin tape stripping on lesional and nonlesional skin of patients with pediatric atopic dermatitis, some of whom also had food allergies. Among other parameters, they measured lipids, proteins, barrier integrity, and the microbiome. They found that nonlesional skin from patients with atopic dermatitis had different characteristics depending on whether the patient also had food allergy. Gene expression analysis also showed elevated type 2 immune signatures in food allergic samples. Their findings reveal unique properties about the epidermis in allergic disease and could lead to the development of biomarkers for food allergy. 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.