Early-onset pediatric atopic dermatitis is TH 2 but also TH 17 polarized in skin

• Published in: Journal of allergy and clinical immunology
• Main Authors: Esaki, Hitokazu, MD, Brunner, Patrick M., MD, Renert-Yuval, Yael, MD, Czarnowicki, Tali, MD, MSc, Huynh, Thy, MD, Tran, Gary, BA, Lyon, Sarah, BA, Rodriguez, Giselle, MD, Immaneni, Supriya, BS, Johnson, Donald B., BS, Bauer, Bruce, MD, Fuentes-Duculan, Judilyn, MD, Zheng, Xiuzhong, MSc, Peng, Xiangyu, MSc, Estrada, Yeriel D., BS, Xu, Hui, MSc, de Guzman Strong, Christina, PhD, Suárez-Fariñas, Mayte, PhD, Krueger, James G., MD, PhD, Paller, Amy S., MD, Guttman-Yassky, Emma, MD, PhD
• Format: Journal Article
• Language: English
• Published: 2016
• Subjects: Allergy and Immunology; OX40L; Keratin 16; skin; Eczema Area and Severity Index; antimicrobials; T H17; Atopic Dermatitis Quickscore; ADQ; pediatric; T H2; EASI; OX40 ligand; Atopic dermatitis; Institutional review board; T H9; PI3; Dendritic cell; Parent's Index of Quality of Life; TEWL; AD; AMP; hARP; TSLPR; Forkhead box P3; Thymic stromal lymphopoietin receptor; Transepidermal water loss; FOXP3; Human acidic ribosomal protein; K16; Peptidase inhibitor 3; IL-19; IL-17; IRB; adult; PIQoL; Antimicrobial peptide; DC
• ISSN: 0091-6749
• DOI: 10.1016/j.jaci.2016.07.013

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 TH 2 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 TH 2 (IL-13, IL-31, and CCL17) and TH 22 (IL-22 and S100As) axes and some TH 1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH 17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH 9/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 TH 2 activation characterizes both, TH 9 and TH 17 are highly activated at disease initiation. Increases in IL-19 levels might link TH 2 and TH 17 activation.