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Cross-sectional study of blood biomarkers of patients with moderate to severe alopecia areata reveals systemic immune and cardiovascular biomarker dysregulation - 11/01/21

Doi : 10.1016/j.jaad.2020.04.138 
Jacob W. Glickman, MA a, Celina Dubin, BA a, Yael Renert-Yuval, MD b, Dante Dahabreh, BA a, Grace W. Kimmel, MD a, Kelsey Auyeung, BA a, Yeriel D. Estrada, BS a, Giselle Singer, BS a, James G. Krueger, MD, PhD b, Ana B. Pavel, PhD a, 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 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 Street, New York, NY 10029.Department of Dermatology and Laboratory of Inflammatory Skin DiseasesIcahn School of Medicine at Mount Sinai5 E 98th StreetNew YorkNY10029s

Abstract

Background

Although there is increased understanding of the alopecia areata (AA) pathogenesis based on studies in scalp tissues, little is known about its systemic profile.

Objective

To evaluate the blood proteomic signature of AA and determine biomarkers associated with increased disease severity.

Methods

In a cross-sectional study, we assessed 350 inflammatory and cardiovascular proteins using OLINK high-throughput proteomics in patients with moderate to severe AA (n = 35), as compared with healthy individuals (n = 36), patients with moderate to severe psoriasis (n = 19), and those with atopic dermatitis (n = 49).

Results

Seventy-four proteins were significantly differentially expressed between AA and control individuals (false discovery rate, <.05) including innate immunity (interleukin [IL] 6/IL-8), T helper (Th) type 1 (interferon [IFN] γ/CXCL9/CXCL10/CXCL11), Th2 (CCL13/CCL17/CCL7), Th17 (CCL20/PI3/S100A12), and cardiovascular-risk proteins (OLR1/OSM/MPO/PRTN3). Eighty-six biomarkers correlated with AA clinical severity (P < .05), including Th1/Th2, and cardiovascular/atherosclerosis-related proteins, including SELP/PGLYRP1/MPO/IL-18/OSM (P < .05). Patients with AA totalis/universalis showed the highest systemic inflammatory tone, including cardiovascular risk biomarkers, compared to control individuals and even to patients with atopic dermatitis and those with psoriasis. The AA profile showed some Th1/Th2 differences in the setting of concomitant atopy.

Limitations

Our analysis was limited to 350 proteins.

Conclusion

This study defined the abnormalities of moderate to severe AA and associated circulatory biomarkers. It shows that AA has systemic immune, cardiovascular, and atherosclerosis biomarker dysregulation, suggesting the need for systemic treatment approaches.

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Key words : Alopecia areata, atherosclerosis, atopic dermatitis, biomarkers, blood, cardiovascular, inflammation, OLINK, proteomics, psoriasis

Abbreviations used : AA, AD, AT, AU, CVD, DEP, FDR, GSVA, IFN, IL, MMP, MPO, SALT, SCORAD, Th


Plan


 Funding sources: None.
 Disclosure: Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from AbbVie, Celgene, Eli Lilly, Janssen, MedImmune/AstraZeneca, Novartis, Pfizer, Regeneron, Vitae, Glenmark, Galderma, Asana, Innovaderm, Dermira, UCB and is 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 Krueger 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. Authors Glickman and Dubin; Dr Renert-Yuval; Author Dahabreh; Dr Kimmel; Authors Auyeung, Estrada, and Singer; and Dr Pavel have no conflicts of interest to declare.
 IRB approval status: Reviewed and approved by Department of Dermatology at the Icahn School of Medicine (approval protocol HS# 14-00436).
 Reprints not available from the authors.


© 2020  American Academy of Dermatology, Inc.. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 84 - N° 2

P. 370-380 - février 2021 Retour au numéro
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