Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Tali Czarnowicki; Helen He; Talia Canter; Joseph Han; Rachel Lefferdink; Taylor Erickson; Stephanie Rangel; Naoya Kameyama; Hyun Je Kim; Ana B. Pavel; Yeriel Estrada; James G. Krueger; Amy S. Paller; Emma Guttman-Yassky

doi:10.1016/j.jaci.2019.09.031

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Tali Czarnowicki, Helen He, Talia Canter, Joseph Han, Rachel Lefferdink, Taylor Erickson, Stephanie Rangel, Naoya Kameyama, Hyun Je Kim, Ana B. Pavel, Yeriel Estrada, James G. Krueger, Amy S. Paller, Emma Guttman-Yassky^*

^*Corresponding author for this work

Dermatology

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

88 Scopus citations

Abstract

Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4⁺/CD8⁺ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)⁺ versus systemic/CLA⁻ T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results: Although CLA⁺ T_H1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA⁺ T_H2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA⁻ T_H2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22). Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.

Original language	English (US)
Pages (from-to)	215-228
Number of pages	14
Journal	Journal of Allergy and Clinical Immunology
Volume	145
Issue number	1
DOIs	https://doi.org/10.1016/j.jaci.2019.09.031
State	Published - Jan 2020

Funding

This study was funded by a grant from the LEO Foundation. The study was also supported by the Northwestern Skin Disease Research Center (NIAMS P30 AR057216) and the Northwestern University Clinical and Translational Sciences (NUCATS) Institute (UL1TR001422).Disclosure of potential conflict of interest: J. G. Krueger has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, Serono, Biogen Idec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. A. S. Paller is an investigator for Galderma, Incyte, Leo, Pfizer, and Regeneron (grants paid to Northwestern University) and has received honoraria related to atopic dermatitis consulting from AbbVie, Asana, Boehringer, Dermavant, Dermira, Eli Lilly, Forte, Galderma, Leo, Matrisys, Menlo Therapeutics, Morphosys/Galapagos, Novartis, Pfizer, Regeneron, and Sanofi-Genzyme. E. Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Asana Biosciences, Celgene, Dermavant, DS Biopharma, Galderma, Glenmark, Innovaderm, Janssen Biotech, Leo Pharma, Novan, Novartis, Pfizer, Ralexar, Regeneron, and Union Therapeutics and is a consultant for Abbvie, Allergan, Amgen, Asana Biosciences, Celgene, Concert, DBV Technologies, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Flx Bio, Galderma, Glenmark, Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Novartis, Pfizer, Regeneron, Sanofi, and Union Therapeutics. The rest of the authors declare that they have no relevant conflicts of interest.

Keywords

Atopic dermatitis
HLA-DR
IFN-γ
IL-13
IL-22
T cell
cutaneous lymphocyte antigen
endotypes
inducible costimulator molecule

ASJC Scopus subject areas

Immunology and Allergy
Immunology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.jaci.2019.09.031

Cite this

Czarnowicki, T., He, H., Canter, T., Han, J., Lefferdink, R., Erickson, T., Rangel, S., Kameyama, N., Kim, H. J., Pavel, A. B., Estrada, Y., Krueger, J. G., Paller, A. S., & Guttman-Yassky, E. (2020). Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. Journal of Allergy and Clinical Immunology, 145(1), 215-228. https://doi.org/10.1016/j.jaci.2019.09.031

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title = "Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood",

abstract = "Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA− T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results: Although CLA+ TH1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ TH2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA− TH2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22). Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.",

keywords = "Atopic dermatitis, HLA-DR, IFN-γ, IL-13, IL-22, T cell, cutaneous lymphocyte antigen, endotypes, inducible costimulator molecule",

author = "Tali Czarnowicki and Helen He and Talia Canter and Joseph Han and Rachel Lefferdink and Taylor Erickson and Stephanie Rangel and Naoya Kameyama and Kim, {Hyun Je} and Pavel, {Ana B.} and Yeriel Estrada and Krueger, {James G.} and Paller, {Amy S.} and Emma Guttman-Yassky",

note = "Publisher Copyright: {\textcopyright} 2019 American Academy of Allergy, Asthma & Immunology",

year = "2020",

month = jan,

doi = "10.1016/j.jaci.2019.09.031",

language = "English (US)",

volume = "145",

pages = "215--228",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Elsevier Inc.",

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Czarnowicki, T, He, H, Canter, T, Han, J, Lefferdink, R, Erickson, T, Rangel, S, Kameyama, N, Kim, HJ, Pavel, AB, Estrada, Y, Krueger, JG, Paller, AS & Guttman-Yassky, E 2020, 'Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood', Journal of Allergy and Clinical Immunology, vol. 145, no. 1, pp. 215-228. https://doi.org/10.1016/j.jaci.2019.09.031

TY - JOUR

T1 - Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

AU - Czarnowicki, Tali

AU - He, Helen

AU - Canter, Talia

AU - Han, Joseph

AU - Lefferdink, Rachel

AU - Erickson, Taylor

AU - Rangel, Stephanie

AU - Kameyama, Naoya

AU - Kim, Hyun Je

AU - Pavel, Ana B.

AU - Estrada, Yeriel

AU - Krueger, James G.

AU - Paller, Amy S.

AU - Guttman-Yassky, Emma

PY - 2020/1

Y1 - 2020/1

N2 - Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA− T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results: Although CLA+ TH1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ TH2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA− TH2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22). Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.

AB - Background: The circulating immune phenotype was defined in adults and young children with early atopic dermatitis (AD), but chronologic changes in the blood of infants and children with AD through adolescence have not been explored. Objective: We sought to compare immune activation and cytokine polarization in the blood of 0- to 5-year-old (n = 39), 6- to 11-year-old (n = 26), 12- to 17-year-old (n = 21) and 18-year-old or older (n = 43) patients with AD versus age-matched control subjects. Methods: Flow cytometry was used to measure IFN-γ, IL-9, IL-13, IL-17, and IL-22 cytokine levels in CD4+/CD8+ T cells, with inducible costimulator molecule and HLA-DR defining midterm and long-term T-cell activation, respectively, within skin-homing/cutaneous lymphocyte antigen (CLA)+ versus systemic/CLA− T cells. Unsupervised clustering differentiated patients based on their blood biomarker frequencies. Results: Although CLA+ TH1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ TH2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA− TH2 frequencies were increased in patients with AD in all age groups, suggesting systemic immune activation with disease chronicity. IL-22 frequencies serially increased from normal levels in infants to highly significant levels in adolescents and adults compared with levels in respective control subjects (P < .01). Unsupervised clustering aligned the AD profiles along an age-related spectrum from infancy to adulthood (eg, inducible costimulator molecule and IL-22). Conclusions: The adult AD phenotype is achieved only in adulthood. Unique cytokine signatures characterizing individual pediatric endotypes might require age-specific therapies. Future longitudinal studies, comparing the profile of patients with cleared versus persistent pediatric AD, might define age-specific changes that predict AD clearance.

KW - Atopic dermatitis

KW - HLA-DR

KW - IFN-γ

KW - IL-13

KW - IL-22

KW - T cell

KW - cutaneous lymphocyte antigen

KW - endotypes

KW - inducible costimulator molecule

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SN - 0091-6749

VL - 145

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JO - Journal of Allergy and Clinical Immunology

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ER -

Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood

Abstract

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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