Minimally invasive skin tape strip RNA-seq identifies novel characteristics of type 2-high atopic dermatitis disease endotype

Publication date: Available online 6 January 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Nathan Dyjack, Elena Goleva, Cydney Rios, Byung Eui Kim, Lianghua Bin, Patricia Taylor, Caroline Bronchick, Clifton F. Hall, Brittany N. Richers, Max A. Seibold, Donald Y. Leung
BackgroundExpression profiling of skin biopsies has established molecular features of the skin in atopic dermatitis (AD). Invasiveness of biopsies has prevented their use in defining individual level AD pathobiological mechanisms (endotypes) in large research studies.ObjectiveTo determine if minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes.MethodsWe sampled non-lesional and lesional skin tape strips and biopsies from adult Caucasian subjects AD patients (18 males, 12 females; age (Mean±SE) 36.3±2.2 yrs) and healthy controls (9 males, 16 females; age (Mean±SE) 34.8±2.2 yrs). Ampliseq whole transcriptome sequencing was performed on extracted RNA. Differential expression, clustering/pathway analyses, immunostaining of skin biopsies, and clinical trait correlations were performed.ResultsSkin 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 (FDR<5%) separated AD from healthy subjects. Agnostic gene set analyses and clustering revealed 50% of AD subjects exhibited a type 2 inflammatory signature (type 2-high endotype) characterized by differential expression of 656 genes including overexpression of IL13, IL4R, CCL22, CCR4 (log2FC=5.5, 2.0, 4.0, and 4.1, respectively), and at a pathway level by T-helper 2/dendritic cell activation. Both expression and immunostaining of skin biopsies indicated this type 2-high group was enriched for inflammatory, type 2-skewed dendritic cells expressing the high affinity IgE receptor (FcεRI). The type 2-high endotype group exhibited more severe disease by both EASI score and body surface area covered by lesions.ConclusionMinimally invasive expression profiling of non-lesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.



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