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

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. We sought to de...

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Vydané v:Journal of allergy and clinical immunology Ročník 141; číslo 4; s. 1298 - 1309
Hlavní autori: Dyjack, Nathan, Goleva, Elena, Rios, Cydney, Kim, Byung Eui, Bin, Lianghua, Taylor, Patricia, Bronchick, Caroline, Hall, Clifton F., Richers, Brittany N., Seibold, Max A., Leung, Donald Y.M.
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States Elsevier Inc 01.04.2018
Elsevier Limited
Predmet:
Adult
Antibiotics
Atopic dermatitis
Biopsy
Case-Control Studies
CCL22 protein
Cell activation
Cross-Sectional Studies
Dendritic cells
Dermatitis
Dermatitis, Atopic - diagnosis
Dermatitis, Atopic - genetics
Disease
Eczema
Epidermis
Female
Gene expression
Gene Expression Profiling - methods
Genetic Markers
Genetic Testing - instrumentation
Genetic Testing - methods
Humans
Immune response
Inflammation
Interleukin 1
Interleukin 13
Interleukin 4 receptors
Lymphocytes T
Male
Ribonucleic acid
RNA
RNA sequencing
Sequence Analysis, RNA
Severity of Illness Index
Skin
Skin diseases
Studies
Surgical Tape
Transcriptome
type 2 immune response
FLG
atopic dermatitis
type 2 immune response
BSA
EASI
RNA-seq
inflammation
FDR
GAGE
IDEC
RNA sequencing
IGA
AD
GO
GSEA
IL-4R
MMP
CCDC80
PC
APC
LC
Skin
SPRR
FC
DC
ISSN:0091-6749, 1097-6825, 1097-6825
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Shrnutí: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. We sought to determine whether minimally invasive skin tape strip transcriptome analysis identifies gene expression dysregulation in AD and molecular disease endotypes. 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. 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. Minimally invasive expression profiling of nonlesional skin reveals stratification in AD molecular pathology by type 2 inflammation that correlates with disease severity.
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ISSN:0091-6749
1097-6825
1097-6825
DOI:10.1016/j.jaci.2017.10.046