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

Donald Y.M. Leung, Agustin Calatroni, Livia S. Zaramela, Petra K. LeBeau, Nathan Dyjack, Kanwaljit Brar, Gloria David, Keli Johnson, Susan Leung, Marco Ramirez-Gama, Bo Liang, Cydney Rios, Michael T. Montgomery, Brittany N. Richers, Clifton F. Hall, Kathryn A. Norquest, John Jung, Irina Bronova, Simion Kreimer, C. Conover Talbot & 7 others Debra Crumrine, Robert N Cole, Peter Elias, Karsten Zengler, Max A. Seibold, Evgeny Berdyshev, Elena Goleva

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Article numbereaav2685
JournalScience translational medicine
Volume11
Issue number480
DOIs
StatePublished - Jan 1 2019

Fingerprint

Food Hypersensitivity
Atopic Dermatitis
Skin
Keratin-16
Keratin-14
Keratin-5
Cornea
Surgical Tape
Metagenomics
Hydroxy Acids
Sphingosine
Ceramides
Firearms
Keratinocytes
Transcriptome
Dendritic Cells
Staphylococcus aureus

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Leung, D. Y. M., Calatroni, A., Zaramela, L. S., LeBeau, P. K., Dyjack, N., Brar, K., ... Goleva, E. (2019). The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype. Science translational medicine, 11(480), [eaav2685]. https://doi.org/10.1126/scitranslmed.aav2685

The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype. / Leung, Donald Y.M.; Calatroni, Agustin; Zaramela, Livia S.; LeBeau, Petra K.; Dyjack, Nathan; Brar, Kanwaljit; David, Gloria; Johnson, Keli; Leung, Susan; Ramirez-Gama, Marco; Liang, Bo; Rios, Cydney; Montgomery, Michael T.; Richers, Brittany N.; Hall, Clifton F.; Norquest, Kathryn A.; Jung, John; Bronova, Irina; Kreimer, Simion; Talbot, C. Conover; Crumrine, Debra; Cole, Robert N; Elias, Peter; Zengler, Karsten; Seibold, Max A.; Berdyshev, Evgeny; Goleva, Elena.

In: Science translational medicine, Vol. 11, No. 480, eaav2685, 01.01.2019.

Research output: Contribution to journalArticle

Leung, DYM, Calatroni, A, Zaramela, LS, LeBeau, PK, Dyjack, N, Brar, K, David, G, Johnson, K, Leung, S, Ramirez-Gama, M, Liang, B, Rios, C, Montgomery, MT, Richers, BN, Hall, CF, Norquest, KA, Jung, J, Bronova, I, Kreimer, S, Talbot, CC, Crumrine, D, Cole, RN, Elias, P, Zengler, K, Seibold, MA, Berdyshev, E & Goleva, E 2019, 'The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype', Science translational medicine, vol. 11, no. 480, eaav2685. https://doi.org/10.1126/scitranslmed.aav2685
Leung, Donald Y.M. ; Calatroni, Agustin ; Zaramela, Livia S. ; LeBeau, Petra K. ; Dyjack, Nathan ; Brar, Kanwaljit ; David, Gloria ; Johnson, Keli ; Leung, Susan ; Ramirez-Gama, Marco ; Liang, Bo ; Rios, Cydney ; Montgomery, Michael T. ; Richers, Brittany N. ; Hall, Clifton F. ; Norquest, Kathryn A. ; Jung, John ; Bronova, Irina ; Kreimer, Simion ; Talbot, C. Conover ; Crumrine, Debra ; Cole, Robert N ; Elias, Peter ; Zengler, Karsten ; Seibold, Max A. ; Berdyshev, Evgeny ; Goleva, Elena. / The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype. In: Science translational medicine. 2019 ; Vol. 11, No. 480.
@article{134d2610cd484125867eb3e21f44e6c6,
title = "The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype",
abstract = "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.",
author = "Leung, {Donald Y.M.} and Agustin Calatroni and Zaramela, {Livia S.} and LeBeau, {Petra K.} and Nathan Dyjack and Kanwaljit Brar and Gloria David and Keli Johnson and Susan Leung and Marco Ramirez-Gama and Bo Liang and Cydney Rios and Montgomery, {Michael T.} and Richers, {Brittany N.} and Hall, {Clifton F.} and Norquest, {Kathryn A.} and John Jung and Irina Bronova and Simion Kreimer and Talbot, {C. Conover} and Debra Crumrine and Cole, {Robert N} and Peter Elias and Karsten Zengler and Seibold, {Max A.} and Evgeny Berdyshev and Elena Goleva",
year = "2019",
month = "1",
day = "1",
doi = "10.1126/scitranslmed.aav2685",
language = "English (US)",
volume = "11",
journal = "Science Translational Medicine",
issn = "1946-6234",
publisher = "American Association for the Advancement of Science",
number = "480",

}

TY - JOUR

T1 - The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype

AU - Leung, Donald Y.M.

AU - Calatroni, Agustin

AU - Zaramela, Livia S.

AU - LeBeau, Petra K.

AU - Dyjack, Nathan

AU - Brar, Kanwaljit

AU - David, Gloria

AU - Johnson, Keli

AU - Leung, Susan

AU - Ramirez-Gama, Marco

AU - Liang, Bo

AU - Rios, Cydney

AU - Montgomery, Michael T.

AU - Richers, Brittany N.

AU - Hall, Clifton F.

AU - Norquest, Kathryn A.

AU - Jung, John

AU - Bronova, Irina

AU - Kreimer, Simion

AU - Talbot, C. Conover

AU - Crumrine, Debra

AU - Cole, Robert N

AU - Elias, Peter

AU - Zengler, Karsten

AU - Seibold, Max A.

AU - Berdyshev, Evgeny

AU - Goleva, Elena

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85061995717&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85061995717&partnerID=8YFLogxK

U2 - 10.1126/scitranslmed.aav2685

DO - 10.1126/scitranslmed.aav2685

M3 - Article

VL - 11

JO - Science Translational Medicine

JF - Science Translational Medicine

SN - 1946-6234

IS - 480

M1 - eaav2685

ER -