Médecine

Paramédical

Autres domaines


S'abonner

The proteomic skin profile of moderate-to-severe atopic dermatitis patients shows an inflammatory signature - 11/02/20

Doi : 10.1016/j.jaad.2019.10.039 
Ana B. Pavel, PhD a, Lisa Zhou, MD a, Aisleen Diaz, BS a, Benjamin Ungar, MD a, Joshua Dan, BA a, Helen He, BS a, Yeriel D. Estrada, BS a, Hui Xu, MS a, Marie Fernandes, PhD a, Yael Renert-Yuval, MD b, James G. Krueger, MD, PhD b, Emma Guttman-Yassky, MD, PhD a,
a Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, New York, New York 
b The Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York 

Correspondence to: Emma Guttman-Yassky MD, PhD, Department of Dermatology and Laboratory of Inflammatory Skin Diseases, Icahn School of Medicine at Mount Sinai, 5 E 98th St, New York, NY, 10029.Department of Dermatology and Laboratory of Inflammatory Skin DiseasesIcahn School of Medicine at Mount Sinai5 E 98th StNew YorkNY10029

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




Le texte complet de cet article est disponible en PDF.

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.
 Funding sources: Olink offered kind support in profiling the proteomics data.
 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.
 IRB approval status: Reviewed and approved by the Icahn School of Medicine at Mount Sinai Institutional Review Board.
 Reprints not available from the authors.


© 2019  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
Ajouter à ma bibliothèque Retirer de ma bibliothèque Imprimer
Export

    Export citations

  • Fichier

  • Contenu

Vol 82 - N° 3

P. 690-699 - mars 2020 Retour au numéro
Article précédent Article précédent
  • Risk of second primary cutaneous and noncutaneous melanoma after cutaneous melanoma diagnosis: A population-based study
  • Kourosh Beroukhim, Aunna Pourang, Daniel B. Eisen
| Article suivant Article suivant
  • An expert panel consensus on opioid-prescribing guidelines for dermatologic procedures
  • Justin M. McLawhorn, Matthew P. Stephany, William E. Bruhn, Lauren D. Crow, Brett M. Coldiron, George J. Hruza, Brian C. Leach, Seaver L. Soon, Daniel P. Friedmann, William G. Stebbins, Travis W. Blalock, Michael S. Graves, Elizabeth M. Billingsley, Thomas J. Knackstedt, Stanley J. Miller, Edward H. Yob, John G. Albertini, Nathalie Zeitouni, Richard A. Krathen, Christopher K. Bichakjian, Nathaniel J. Jellinek, C. William Hanke, Faramarz H. Samie, Margaret W. Mann, John A. Carucci, Rohit Kakar, Drew K. Saylor, Scott W. Fosko, Arisa E. Ortiz, William B. Henghold, Thomas A. Jennings, DiAnne S. Davis, Mary E. Maloney, Natalie M. Curcio, Ramona Behshad, Whitney D. Tope, Holly McCoppin, Jarad I. Levin, Lindsey Collins, Thomas Stasko, Opioid-Prescribing in Dermatology Workgroup

Bienvenue sur EM-consulte, la référence des professionnels de santé.
L’accès au texte intégral de cet article nécessite un abonnement.

Déjà abonné à cette revue ?

Mon compte


Plateformes Elsevier Masson

Déclaration CNIL

EM-CONSULTE.COM est déclaré à la CNIL, déclaration n° 1286925.

En application de la loi nº78-17 du 6 janvier 1978 relative à l'informatique, aux fichiers et aux libertés, vous disposez des droits d'opposition (art.26 de la loi), d'accès (art.34 à 38 de la loi), et de rectification (art.36 de la loi) des données vous concernant. Ainsi, vous pouvez exiger que soient rectifiées, complétées, clarifiées, mises à jour ou effacées les informations vous concernant qui sont inexactes, incomplètes, équivoques, périmées ou dont la collecte ou l'utilisation ou la conservation est interdite.
Les informations personnelles concernant les visiteurs de notre site, y compris leur identité, sont confidentielles.
Le responsable du site s'engage sur l'honneur à respecter les conditions légales de confidentialité applicables en France et à ne pas divulguer ces informations à des tiers.