Tali Czarnowicki1, Helen He2, Talia Canter3, Joseph Han2, Rachel Lefferdink3, Taylor Erickson3, Stephanie Rangel3, Naoya Kameyama2, Hyun Je Kim2, Ana B Pavel2, Yeriel Estrada2, James G Krueger4, Amy S Paller3, Emma Guttman-Yassky5. 1. 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. 2. Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. 3. Departments of Dermatology and Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Ill. 4. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. 5. Department of Dermatology and the Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY. Electronic address: emma.guttman@mountsinai.org.
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.
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: Judith L Thijs; Ian Strickland; Carla A F M Bruijnzeel-Koomen; Stefan Nierkens; Barbara Giovannone; Edward F Knol; Eszter Csomor; Bret R Sellman; Tomas Mustelin; Matthew A Sleeman; Marjolein S de Bruin-Weller; Athula Herath; Julia Drylewicz; Richard D May; DirkJan Hijnen Journal: J Allergy Clin Immunol Date: 2018-02-02 Impact factor: 10.793
Authors: Floor Weerkamp; Edwin F E de Haas; Brigitta A E Naber; W Marieke Comans-Bitter; Ad J J C Bogers; Jacques J M van Dongen; Frank J T Staal Journal: J Allergy Clin Immunol Date: 2005-04 Impact factor: 10.793
Authors: Jungang Xie; Larisa C Lotoski; Rishma Chooniedass; Ruey-Chyi Su; F Estelle R Simons; Joel Liem; Allan B Becker; Jude Uzonna; Kent T HayGlass Journal: PLoS One Date: 2012-10-11 Impact factor: 3.240
Authors: Sarah M Engle; Ching-Yun Chang; Benjamin J Ulrich; Allyson Satterwhite; Tristan Hayes; Kim Robling; Sean E Sissons; Jochen Schmitz; Robert S Tepper; Mark H Kaplan; Jonathan T Sims Journal: Clin Exp Immunol Date: 2022-05-12 Impact factor: 4.330
Authors: El-Bdaoui Haddad; Sonya L Cyr; Kazuhiko Arima; Robert A McDonald; Noah A Levit; Frank O Nestle Journal: Dermatol Ther (Heidelb) Date: 2022-05-21
Authors: Yael Renert-Yuval; Ester Del Duca; Ana B Pavel; Milie Fang; Rachel Lefferdink; Jianni Wu; Aisleen Diaz; Yeriel D Estrada; Talia Canter; Ning Zhang; Annette Wagner; Sarah Chamlin; James G Krueger; Emma Guttman-Yassky; Amy S Paller Journal: J Allergy Clin Immunol Date: 2021-01-13 Impact factor: 14.290
Authors: Sarah M Engle; Ching-Yun Chang; Benjamin J Ulrich; Allyson Satterwhite; Tristan Hayes; Kim Robling; Sean E Sissons; Jochen Schmitz; Robert S Tepper; Mark H Kaplan; Jonathan T Sims Journal: Clin Exp Immunol Date: 2021-11-30 Impact factor: 5.732
Authors: Ana B Pavel; Yael Renert-Yuval; Jianni Wu; Ester Del Duca; Aisleen Diaz; Rachel Lefferdink; Milie M Fang; Talia Canter; Stephanie M Rangel; Ning Zhang; James G Krueger; Amy S Paller; Emma Guttman-Yassky Journal: Allergy Date: 2020-08-20 Impact factor: 14.710
Authors: A Wollenberg; A Blauvelt; E Guttman-Yassky; M Worm; C Lynde; J-P Lacour; L Spelman; N Katoh; H Saeki; Y Poulin; A Lesiak; L Kircik; S H Cho; P Herranz; M J Cork; K Peris; L A Steffensen; B Bang; A Kuznetsova; T N Jensen; M L Østerdal; E L Simpson Journal: Br J Dermatol Date: 2020-12-30 Impact factor: 9.302