The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature - 11/02/20
Abstract |
Background |
Moderate-to-severe atopic dermatitis (AD) is increasingly recognized as a systemic disease, largely due to proteomic blood studies. There are growing efforts to develop AD biomarkers using minimal tissues.
Objective |
To characterize the AD skin proteomic signature and its relationship with the blood proteome and genomic skin profile in the same individuals.
Methods |
We evaluated lesional and nonlesional biopsy samples and blood from 20 individuals with moderate-to-severe AD and 28 healthy individuals using Olink Proteomics (Uppsala, Sweden), using 10 μg/10 μL for skin and blood and RNA sequencing of the skin.
Results |
The AD skin proteome demonstrated significant upregulation in lesional and even in nonlesional skin compared with controls in inflammatory markers (matrix metalloproteinase 12; T-helper cell [Th]2/interleukin [IL]-1 receptor-like 1[IL1RL1]/IL-33R, IL-13, chemokine [C-C motif] ligand [CCL] 17; Th1/C-X-C motif chemokine 10; Th17/Th22/PI3, CCL20, S100A12), and in cardiovascular-associated proteins (E-selectin, matrix metalloproteinases, platelet growth factor, myeloperoxidase, fatty acid binding protein 4, and vascular endothelial growth factor A; false discovery rate, <0.05). Skin proteins demonstrated much higher and significant upregulations (vs controls) compared with blood, suggesting a skin source for the inflammatory/cardiovascular profile. Gene and protein expressions were correlated (r = 0.410, P < .001), with commonly upregulated inflammatory and cardiovascular risk-associated products, suggesting protein translation in skin.
Limitations |
Our analysis was limited to 354 proteins.
Conclusions |
The AD skin proteome shows an inflammatory and cardiovascular signature even in nonlesional skin, emphasizing the need for proactive treatment. Skin proteomics presents a sensitive option for biomarker monitoring.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : atherosclerosis, atopic dermatitis, biomarkers, blood, cardiovascular, inflammatory, Olink, proteomics, skin
Abbreviations used : AD, CCL, CVD, CXCL, DEP, EASI, FABP4, FCH, FDR, FLT3LG, HMOX1, IL, IL-1RL1, LOX-1, LTBR, MCP-1, MPO, mRNA, OSM, PGF, RETN, RNAseq, Th, SELE, SCORAD, TNFSF10/TRAIL, VEGFA
Plan
Drs Pavel, Zhou, Diaz, and Ungar contributed equally to this work. |
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Funding sources: Olink offered kind support in profiling the proteomics data. |
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Conflicts of interest: Authors Pavel, Ungar, Estrada, Xu, and Fernandes are employees of Mount Sinai. Dr Krueger is an employee of The Rockefeller University and has received research funds from Pfizer, Amgen, Janssen, Lilly, Merck, Novartis, Kadmon, Dermira, Boehringer, Innovaderm, Kyowa, BMS, 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 the institution) from AbbVie, Almirall, AnaptysBio, Boehringer-Ingelheim, Celgene, Dermavant, DS Biopharma, Eli Lilly, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Novan, Pfizer, Regeneron, Ralexar, Glenmark, Galderma, Asana, Innovaderm, LEO Pharma, Sienna Biopharm, Union Therapeutics, and UCB and is also a consultant for Sanofi Aventis, Regeneron, Cara Therapeutics, Celgene, Concert, Amgen, Boehringer-Ingelheim, DBV, Dermira, DS Biopharma, EMD Serono, Escalier, Flx Bio, Galderma, Glenmark, Incyte, Kyowa Kirin, Novartis, Pfizer, LEO Pharma, AbbVie, Eli Lilly, Kyowa, Mitsubishi Tanabe, Asana Biosciences, Sienna Biopharm, and Union Therapeutics. Authors Zhou, Diaz, Dan, He, and Renert-Yuval declare no other relevant conflicts of interest. |
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IRB approval status: Reviewed and approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board. |
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Reprints not available from the authors. |
Vol 82 - N° 3
P. 690-699 - mars 2020 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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