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; Debra Crumrine; Robert N. Cole; Peter Elias; Karsten Zengler; Max A. Seibold; Evgeny Berdyshev; Elena Goleva

doi:10.1126/scitranslmed.aav2685

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 TalbotDebra Crumrine, Robert N. Cole, Peter Elias, Karsten Zengler, Max A. Seibold, Evgeny Berdyshev, Elena Goleva

School of Medicine

Research output: Contribution to journal › Article › peer-review

60 Scopus citations

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 language	English (US)
Article number	eaav2685
Journal	Science translational medicine
Volume	11
Issue number	480
DOIs	https://doi.org/10.1126/scitranslmed.aav2685
State	Published - 2019

ASJC Scopus subject areas

General Medicine

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10.1126/scitranslmed.aav2685

Cite this

Leung, D. Y. M., Calatroni, A., Zaramela, L. S., LeBeau, P. K., Dyjack, N., Brar, K., David, G., Johnson, K., Leung, S., Ramirez-Gama, M., Liang, B., Rios, C., Montgomery, M. T., Richers, B. N., Hall, C. F., Norquest, K. A., Jung, J., Bronova, I., Kreimer, S., ... Goleva, E. (2019). The nonlesional skin surface distinguishes atopic dermatitis with food allergy as a unique endotype. Science translational medicine, 11(480), Article eaav2685. https://doi.org/10.1126/scitranslmed.aav2685

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

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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",

note = "Publisher Copyright: Copyright {\textcopyright} 2019 The Authors, some rights reserved.",

year = "2019",

doi = "10.1126/scitranslmed.aav2685",

language = "English (US)",

volume = "11",

journal = "Science translational medicine",

issn = "1946-6234",

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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

Y1 - 2019

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.

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IS - 480

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ER -

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

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