Early-onset pediatric atopic dermatitis is T2 but also T17 polarized in skin.
Esaki Hitokazu,Brunner Patrick M,Renert-Yuval Yael,Czarnowicki Tali,Huynh Thy,Tran Gary,Lyon Sarah,Rodriguez Giselle,Immaneni Supriya,Johnson Donald B,Bauer Bruce,Fuentes-Duculan Judilyn,Zheng Xiuzhong,Peng Xiangyu,Estrada Yeriel D,Xu Hui,de Guzman Strong Christina,Suárez-Fariñas Mayte,Krueger James G,Paller Amy S,Guttman-Yassky Emma
The Journal of allergy and clinical immunology
BACKGROUND:Atopic dermatitis (AD) affects 15% to 25% of children and 4% to 7% of adults. Paradigm-shifting discoveries about AD have been based on adult biomarkers, reflecting decades of disease activity, although 85% of cases begin by 5 years. Blood phenotyping shows only T2 skewing in patients with early-onset pediatric AD, but alterations in early pediatric skin lesions are unknown, limiting advancement of targeted therapies. OBJECTIVE:We sought to characterize the early pediatric AD skin phenotype and its differences from pediatric control subjects and adults with AD. METHODS:Using immunohistochemistry and quantitative real-time PCR, we assessed biopsy specimens from 19 children with AD younger than 5 years within 6 months of disease onset in comparison with adults with AD or psoriasis and pediatric and adult control subjects. RESULTS:In lesional skin children showed comparable or greater epidermal hyperplasia (thickness and keratin 16) and cellular infiltration (CD3, CD11c, and FcεRI) than adults with AD. Similar to adults, strong activation of the T2 (IL-13, IL-31, and CCL17) and T22 (IL-22 and S100As) axes and some T1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of T17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), T9/IL-9, IL-33, and innate markers (IL-8) than adults (P < .02). Despite the characteristic downregulation in adult patients with AD, filaggrin expression was similar in children with AD and healthy children. Nonlesional skin in pediatric patients with AD showed higher levels of inflammation (particularly IL-17A and the related molecules IL-19 and LL37) and epidermal proliferation (keratin 16 and S100As) markers (P < .001). CONCLUSION:The skin phenotype of new-onset pediatric AD is substantially different from that of adult AD. Although excess T2 activation characterizes both, T9 and T17 are highly activated at disease initiation. Increases in IL-19 levels might link T2 and T17 activation.