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Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood.
J Allergy Clin Immunol 2020; 145(1):215-228JA

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.

Authors+Show Affiliations

Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY.Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill.Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: emma.guttman@mountsinai.org.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31626841

Citation

Czarnowicki, Tali, et al. "Evolution of Pathologic T-cell Subsets in Patients With Atopic Dermatitis From Infancy to Adulthood." The Journal of Allergy and Clinical Immunology, vol. 145, no. 1, 2020, pp. 215-228.
Czarnowicki T, He H, Canter T, et al. Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. J Allergy Clin Immunol. 2020;145(1):215-228.
Czarnowicki, T., He, H., Canter, T., Han, J., Lefferdink, R., Erickson, T., ... Guttman-Yassky, E. (2020). Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood. The Journal of Allergy and Clinical Immunology, 145(1), pp. 215-228. doi:10.1016/j.jaci.2019.09.031.
Czarnowicki T, et al. Evolution of Pathologic T-cell Subsets in Patients With Atopic Dermatitis From Infancy to Adulthood. J Allergy Clin Immunol. 2020;145(1):215-228. PubMed PMID: 31626841.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2019/10/15/ PY - 2019/04/21/received PY - 2019/08/23/revised PY - 2019/09/12/accepted PY - 2021/01/01/pmc-release PY - 2019/10/19/pubmed PY - 2019/10/19/medline PY - 2019/10/19/entrez 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 SP - 215 EP - 228 JF - The Journal of allergy and clinical immunology JO - J. Allergy Clin. Immunol. VL - 145 IS - 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. SN - 1097-6825 UR - https://www.unboundmedicine.com/medline/citation/31626841/Evolution_of_pathologic_T-cell_subsets_in_atopic_dermatitis_from_infancy_to_adulthood L2 - https://linkinghub.elsevier.com/retrieve/pii/S0091-6749(19)31319-3 DB - PRIME DP - Unbound Medicine ER -