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Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood
Open accessAbstract
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 H 1 frequencies were significantly lower in infants with AD versus all older patients (P < .01), frequencies of CLA+ T H 2 T cells were similarly expanded across all AD age groups compared with control subjects (P < .05). After infancy, CLA- T H 2 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.
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“there is increasing evidence that the IL-23–IL-17 axis as well as IL-36 (see above) may have a role, at least in some AD subtypes such as the so-called intrinsic form and in Asian patients73,103,117,123–125.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [124]
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“The sequential and/or cumulative immunological events that underlie the complex clinical phenotype are key to understanding the value of targeted therapies for distinct pathways such as TH2, TH17 and/or TH22 response124,125.”
From Atopic dermatitis: an expanding therapeutic pipeline for a complex disease (2022) · cites this paper as [124]
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Self-citation
Metadata
- Authors
- 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.
- Affiliations
- Rockefeller University (US)
- Icahn School of Medicine at Mount Sinai (US)
- Northwestern University (US)
- ORCID
- Venue
- Journal of Allergy and Clinical Immunology
- Publisher
- Elsevier BV
- Published
- 2020-01
- Volume
- 145
- Issue
- 1
- Pages
- 215-228
- ISSN
- 0091-6749 (ISSN-L)
- PMC
- PMC6957229
- OpenAlex
- W2980556682
- Cited by
- 118
- References
- 90
- Citations by year
- 2026: 9 · 2025: 22 · 2024: 19 · 2023: 19 · 2022: 17 · 2021: 22 · 2020: 10
- FWCI
- 12.34
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Journal of Allergy and Clinical Immunology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Seoul National University Open Repository (Seoul National University) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases
- Topics
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Asthma and respiratory diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- atopic dermatitis, T cell subsets, age-related immune changes, cutaneous lymphocyte antigen, skin-homing T cells, Th1/Th2 balance, IL-22, IL-13, IL-17, IL-9, interferon-gamma, HLA-DR, T cell activation, chronicity, infants and children
- MeSH terms
- Adolescent, Adult, Child, Child, Preschool, Dermatitis, Atopic, Female, HLA-DR Antigens, Humans, Infant, Infant, Newborn, Male, Cytokines, Th1 Cells, Th2 Cells
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