Minimally invasive skin tape strip RNA sequencing identifies novel characteristics of the type 2–high atopic dermatitis disease endotype - 05/04/18
, Donald Y.M. Leung, MD, PhD b, d, ⁎, ‡ 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.
Le texte complet de cet article est disponible en PDF.Key words : Skin, atopic dermatitis, RNA sequencing, type 2 immune response, inflammation
Abbreviations : AD, APC, BSA, CCDC80, DC, EASI, FC, FDR, FLG, GAGE, GO, GSEA, IDEC, IGA, IL-4R, LC, MMP, PC, RNA-seq, SPRR
Plan
| Supported in part by National Institutes of Health (NIH)/National Institute of Arthritis and Musculoskeletal Diseases (NIAMS) grant R01 AR41256, NIH/National Institute of Allergy and Infectious Diseases (NIAID) grant U19 AI117673, NIH/National Center for Research Resources (NCRR) grant UL1 RR025780 and the Edelstein Family Chair of Pediatric Allergy-Immunology at National Jewish Health. To M.A.S.: NIH grant nos. P01 HL132821-01A1, R01 HL135156-01, R01 MD010443-02, and R01 HL128439-03; and Department of Defense grant no. W81WH-16-2-0018. |
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| Disclosure of potential conflict of interest: N. Dyjack's institution has received funding from the Atopic Dermatitis Research Network (ADRN) and NIAID grant U19 AI117673. E. Goleva's institution has received grant funding from the National Institutes of Health (NIH). L. Bin has an NIH grant (NIH/NIAIDU19 Al117673). B. N. Richers' institution has received grant funding from the NIH. M. A. Seibold's institution has received grant funds and travel support from the NIH and has a grant pending from MedImmune and the NIH (to identify type 2 high biomarkers in asthma); he has received support from Genentech for lecturing and travel. D. Y. Leung's institution has received funds from a National Institute of Allergy and Infectious Diseases (NIAID)/NIH grant and has grants pending from Incyte and Pfizer; he has consulted for Regeneron and Sanofi and received speaker fees from Regeneron. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 4
P. 1298-1309 - avril 2018 Retour au numéro
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