Early-onset pediatric atopic dermatitis is characterized by TH2/TH17/TH22-centered inflammation and lipid alterations - 06/06/18
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Abstract |
Background |
Although atopic dermatitis (AD) often starts in early childhood, detailed tissue profiling of early-onset AD in children is lacking, hindering therapeutic development for this patient population with a particularly high unmet need for better treatments.
Objective |
We sought to globally profile the skin of infants with AD compared with that of adults with AD and healthy control subjects.
Methods |
We performed microarray, RT-PCR, and fluorescence microscopy studies in infants and young children (<5 years old) with early-onset AD (<6 months disease duration) compared with age-matched control subjects and adults with longstanding AD.
Results |
Transcriptomic analyses revealed profound differences between pediatric patients with early-onset versus adult patients with longstanding AD in not only lesional but also nonlesional tissues. Although both patient populations harbored TH2-centered inflammation, pediatric AD also showed significant TH17/TH22 skewing but lacked the TH1 upregulation that characterizes adult AD. Pediatric AD exhibited relatively normal expression of epidermal differentiation and cornification products, which is downregulated in adults with AD. Defects in the lipid barrier (eg, ELOVL fatty acid elongase 3 [ELOVL3] and diacylglycerol o-acyltransferase 2 [DGAT2]) and tight junction regulation (eg, claudins 8 and 23) were evident in both groups. However, some lipid-associated mediators (eg, fatty acyl-CoA reductase 2 and fatty acid 2-hydroxylase) showed preferential downregulation in pediatric AD, and lipid barrier genes (FA2H and DGAT2) showed inverse correlations with transepidermal water loss, a functional measure of the epidermal barrier.
Conclusions |
Skin samples from children and adult patients with AD share lipid metabolism and tight junction alterations, but epidermal differentiation complex defects are only present in adult AD, potentially resulting from chronic immune aberration that is not yet present in early-onset disease.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, pediatric, infant, skin barrier, skin inflammation
Abbreviations used : AD, CLDN, DEG, EDC, ELOVL, EREG, FLG, KYNU, LCE, STAT, TEWL
Plan
Supported by a research grant from the LEO Foundation. P.M.B. was supported in part by grant no. UL1 TR0001866 from the National Center for Advancing Translational Sciences (NCATS), National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program. |
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Disclosure of potential conflict of interest: P. M. Brunner received payment for lectures from Sanofi, Pfizer, and LEO Pharma. J. G. Krueger's institution and he personally received fees from Novartis, Pfizer, Amgen, Boehringer, Janssen, AbbVie, Leo Pharma, Acros; he personally received personal from Lilly, Biogen Idec, Escalier, Roche, Valeant, Allergan, Aurigene, and Asana; and his institution received personal fees from Innovaderm, BMS, Paraxel, Vitae, Kineta, Regeneron, Novan, BiogenMA, Sienna, UCB, and Allergan. A. S. Paller received consultancy fees from Dermira, Eli Lily, Expanscience, Galderma Laboratories, Menlo Therapeutics, Novartis Pharmaceuticals, Pfizer, Pierre Fabre Dermatologie, Regeneron/Sanofi, and Valeant Pharmaceuticals, and her institution received grants from Anacor, Astellas, and the Leo Foundation for other works. E. Guttman-Yassky personally received board membership from Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, Medimmune, Celgene, Anacor, Leo Pharma, AnaptysBio, Celsus, Dermira, Galderma, Novartis, Pfizer, Vitae, Glenmark, AbbVie, and Asana Biosciences and consultancy fees from Regeneron, Sanofi Aventis, Medimmune, Celgene, Stiefel/GlaxoSmithKline, Celsus, BMS, Amgen, Drais, AbbVie, Anacor, AnaptysBio, Dermira, Galderma, Leo Pharma, Novartis, Pfizer, Vitae, Mitsubishi Tanabe, Eli Lilly, Glenmark, and Asana Biosciences, and her institution received grants for other works from Regeneron, Celgene, BMS, Janssen, Dermira, Leo Pharma, Merck, Novartis, and UCB. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 141 - N° 6
P. 2094-2106 - juin 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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