The blood proteomic signature of early-onset pediatric atopic dermatitis shows systemic inflammation and is distinct from adult long-standing disease - 27/07/19
Abstract |
Background |
Despite increasing evidence that adults with long-standing atopic dermatitis (AD) have systemic inflammation, little is known about systemic inflammation in recent-onset early pediatric AD.
Objective |
To analyze blood inflammatory proteins of early pediatric AD.
Methods |
Using high-throughput proteomics (proximity extension assay), we assessed 257 inflammatory and cardiovascular risk proteins in the blood of 30 children with moderate to severe AD younger than 5 years of age (within 6 months of onset) compared with age-matched pediatric control individuals and adult patients with AD.
Results |
In pediatric AD blood, T helper (Th) type 2 (CCL13, CCL22) and Th17 (peptidase inhibitor-3/elafin) markers were increased, together with markers of tissue remodeling (matrix metalloproteinases 3/9/10, urokinase receptor), endothelial activation (E-selectin), T-cell activation (IL2RA), neutrophil activation (myeloperoxidase), lipid metabolism (FABP4), and growth factors (FGF21, transforming growth factor-α). Total numbers of dysregulated proteins were smaller in pediatric AD (n = 22) than in adult AD (n = 61). Clinical severity scores were positively correlated with receptors for interleukins 33 and 36 and inversely correlated with some Th1 markers (interferon gamma, CXCL11).
Limitations |
Different baseline expression levels in healthy pediatric vs adult samples.
Conclusions |
Within months of pediatric AD onset, systemic immune activation is present, with Th2/Th17 skewing but otherwise different proteomic patterns from adult AD. Future correlation of proteomic patterns with disease course, comorbidity development, and drug response may yield predictive biomarkers.
Le texte complet de cet article est disponible en PDF.Key words : Atopic dermatitis, infant, multiplex assay, Olink, pediatric, peripheral blood, proximity extension assay
Abbreviations used : AD, BSA, EASI, FDR, IFN, MMP, PI3, SCORAD, SELE, TARC, TEWL, TGF
Plan
| Drs Guttman-Yassky and Paller contributed equally to this article. |
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| Supported by a research grant from Galderma SA. PMB was supported in part by grant no. UL1 TR00043 from the National Center for Advancing Translational Sciences, National Institutes of Health Clinical and Translational Science Award program. NP was supported by a Dermatology Fellowship Grant from Pfizer. The study was also supported by the Northwestern Skin Disease Research Center (National Institute of Arthritis and Musculoskeletal and Skin Diseases P30 AR057216) and the Northwestern University Clinical and Translational Sciences Institute (UL1TR001422). |
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| Disclosure: Dr Brunner has received personal fees from LEO Pharma, Pfizer, Sanofi Genzyme, Celgene, and Lilly. Dr Puar received fellowship support from Pfizer. Dr Krueger is an employee of Rockefeller University and has received research support (grants paid to his institution) and/or personal fees from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, Bristol-Myers Squibb, Serono, Biogen Idec, Delenex, AbbVie, Sanofi, Baxter, Paraxel, Xenoport, and Kineta. Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to her institution) from AbbVie, Celgene, Eli Lilly, Janssen, MedImmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, and Union Chimique Belge (UCB). Dr Guttman-Yassky is also a consultant for Sanofi Aventis, Regeneron, Stiefel/GlaxoSmithKline, MedImmune, Celgene, Anacor, AnaptysBio, Dermira, Galderma, Glenmark, Novartis, Pfizer, Vitae, Leo Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, and Promius. Dr Paller is an investigator for Galderma, Incyte, Leo, Pfizer, and Regeneron (grants paid to Northwestern University) and has received honoraria related to atopic dermatitis consulting from AbbVie, Asana, Boehringer, Dermavant, Dermira, Eli Lilly, Forte, Galderma, Leo, MatriSys, Menlo Therapeutics, MorphoSys/Galapagos, Novartis, Pfizer, Regeneron, and Sanofi-Genzyme. Drs He, Pavel, Czarnowicki, Lefferdink, Erickson, Canter, Rangel, Malik, and Estrada have no conflicts of interest to declare. |
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| Reprints not available from the authors. |
Vol 81 - N° 2
P. 510-519 - août 2019 Retour au numéro
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