Hitokazu Esaki1, Patrick M Brunner2, Yael Renert-Yuval3, Tali Czarnowicki2, Thy Huynh4, Gary Tran4, Sarah Lyon4, Giselle Rodriguez4, Supriya Immaneni4, Donald B Johnson5, Bruce Bauer5, Judilyn Fuentes-Duculan2, Xiuzhong Zheng2, Xiangyu Peng3, Yeriel D Estrada3, Hui Xu3, Christina de Guzman Strong6, Mayte Suárez-Fariñas7, James G Krueger2, Amy S Paller4, Emma Guttman-Yassky8. 1. Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. 2. Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. 3. Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY. 4. Department of Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Ill. 5. NorthShore University HealthSystem, University of Chicago Pritzker School of Medicine, Northbrook, Ill. 6. Division of Biology and Biomedical Sciences, Washington University, St Louis, Mo. 7. Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY; Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY; Department of Genetics and Genomics Science, Icahn Institute for Genomics and Multiscale Biology, New York, NY. 8. Department of Dermatology and Laboratory for Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, NY; Laboratory for Investigative Dermatology, Rockefeller University, New York, NY. Electronic address: Emma.Guttman@mountsinai.org.
Abstract
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 TH2 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 TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/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 TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation. Copyright Â
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 TH2 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 TH2 (IL-13, IL-31, and CCL17) and TH22 (IL-22 and S100As) axes and some TH1 skewing (IFN-γ and CXCL10) were present. Children showed significantly higher induction of TH17-related cytokines and antimicrobials (IL-17A, IL-19, CCL20, LL37, and peptidase inhibitor 3/elafin), TH9/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 TH2 activation characterizes both, TH9 and TH17 are highly activated at disease initiation. Increases in IL-19 levels might link TH2 and TH17 activation. Copyright Â
Authors: Sharon A McGrath-Morrow; Roland Ndeh; Joseph M Collaco; Amy K Poupore; Dustin Dikeman; Qiong Zhong; Benjamin D Singer; Franco D'Alessio; Alan Scott Journal: Cytokine Date: 2017-06-16 Impact factor: 3.861
Authors: Michael R Williams; Stephen K Costa; Livia S Zaramela; Shadi Khalil; Daniel A Todd; Heather L Winter; James A Sanford; Alan M O'Neill; Marc C Liggins; Teruaki Nakatsuji; Nadja B Cech; Ambrose L Cheung; Karsten Zengler; Alexander R Horswill; Richard L Gallo Journal: Sci Transl Med Date: 2019-05-01 Impact factor: 17.956
Authors: Wendy F Davidson; Donald Y M Leung; Lisa A Beck; Cecilia M Berin; Mark Boguniewicz; William W Busse; Talal A Chatila; Raif S Geha; James E Gern; Emma Guttman-Yassky; Alan D Irvine; Brian S Kim; Heidi H Kong; Gideon Lack; Kari C Nadeau; Julie Schwaninger; Angela Simpson; Eric L Simpson; Jonathan M Spergel; Alkis Togias; Ulrich Wahn; Robert A Wood; Judith A Woodfolk; Steven F Ziegler; Marshall Plaut Journal: J Allergy Clin Immunol Date: 2019-01-09 Impact factor: 10.793