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J Allergy Clin Immunol. 2018 Apr;141(4):1298-1309. doi: 10.1016/j.jaci.2017.10.046. Epub 2018 Jan 6.

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

Author information

1
Center for Genes, Environment, and Health, National Jewish Health, Denver, Colo.
2
Department of Pediatrics, National Jewish Health, Denver, Colo.
3
Center for Genes, Environment, and Health, National Jewish Health, Denver, Colo; Department of Pediatrics, National Jewish Health, Denver, Colo; Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Aurora, Colo. Electronic address: seiboldm@njhealth.org.
4
Department of Pediatrics, National Jewish Health, Denver, Colo; Department of Pediatrics, University of Colorado Denver, Aurora, Colo. Electronic address: Leungd@NJHealth.org.

Abstract

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 FcεRI. 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.

KEYWORDS:

RNA sequencing; Skin; atopic dermatitis; inflammation; type 2 immune response

PMID:
29309794
PMCID:
PMC5892844
DOI:
10.1016/j.jaci.2017.10.046
[Indexed for MEDLINE]
Free PMC Article

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