Evolution of pathologic T-cell subsets in patients with atopic dermatitis from infancy to adulthood - 05/01/20
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Atopic dermatitis, endotypes, T cell, cutaneous lymphocyte antigen, IL-13, IL-22, IFN-γ, inducible costimulator molecule, HLA-DR
Abbreviations used : AD, CLA, EASI, FCH, ICOS, ILC, TC, Tcm, Tem, TEWL, Treg
Plan
| 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). |
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| 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. |
Vol 145 - N° 1
P. 215-228 - janvier 2020 Retour au numéro
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