An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata

Jacob W. Glickman; Celina Dubin; Dante Dahabreh; Joseph Han; Ester Del Duca; Yeriel D. Estrada; Ning Zhang; Grace W. Kimmel; Giselle Singer; James G. Krueger; Ana B. Pavel; Emma Guttman-Yassky

doi:10.1111/all.14814

An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata

Jacob W. Glickman, Celina Dubin, Dante Dahabreh, Joseph Han, Ester Del Duca, Yeriel D. Estrada, Ning Zhang, Grace W. Kimmel, Giselle Singer, James G. Krueger, Ana B. Pavel, Emma Guttman-Yassky

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

Background: Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity. Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT). Results: A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp (p <.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (p <.05). AA scalp demonstrated significantly greater biomarker dysregulation compared to blood. An integrated multivariate approach combining scalp and serum biomarkers improved correlations with disease severity/SALT. Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.

Original language	English
Pages (from-to)	3053-3065
Number of pages	13
Journal	Allergy: European Journal of Allergy and Clinical Immunology
Volume	76
Issue number	10
DOIs	https://doi.org/10.1111/all.14814
State	Published - Oct 2021

Keywords

OLINK
RNAseq
alopecia areata
bioinformatics
biomarkers

Access to Document

10.1111/all.14814

Cite this

Glickman, J. W., Dubin, C., Dahabreh, D., Han, J., Del Duca, E., Estrada, Y. D., Zhang, N., Kimmel, G. W., Singer, G., Krueger, J. G., Pavel, A. B., & Guttman-Yassky, E. (2021). An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata. Allergy: European Journal of Allergy and Clinical Immunology, 76(10), 3053-3065. https://doi.org/10.1111/all.14814

@article{311a6415eddd4ad9a9d6d20909afc7b2,

title = "An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata",

abstract = "Background: Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity. Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT). Results: A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp (p <.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (p <.05). AA scalp demonstrated significantly greater biomarker dysregulation compared to blood. An integrated multivariate approach combining scalp and serum biomarkers improved correlations with disease severity/SALT. Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.",

keywords = "OLINK, RNAseq, alopecia areata, bioinformatics, biomarkers",

author = "Glickman, {Jacob W.} and Celina Dubin and Dante Dahabreh and Joseph Han and {Del Duca}, Ester and Estrada, {Yeriel D.} and Ning Zhang and Kimmel, {Grace W.} and Giselle Singer and Krueger, {James G.} and Pavel, {Ana B.} and Emma Guttman-Yassky",

note = "Funding Information: We acknowledge the Department of Dermatology at the Icahn School of Medicine for its contribution to this study. Publisher Copyright: {\textcopyright} 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.",

year = "2021",

month = oct,

doi = "10.1111/all.14814",

language = "English",

volume = "76",

pages = "3053--3065",

journal = "Allergy: European Journal of Allergy and Clinical Immunology",

issn = "0105-4538",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "10",

}

Glickman, JW, Dubin, C, Dahabreh, D, Han, J, Del Duca, E, Estrada, YD, Zhang, N, Kimmel, GW, Singer, G, Krueger, JG, Pavel, AB & Guttman-Yassky, E 2021, 'An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata', Allergy: European Journal of Allergy and Clinical Immunology, vol. 76, no. 10, pp. 3053-3065. https://doi.org/10.1111/all.14814

TY - JOUR

T1 - An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata

AU - Glickman, Jacob W.

AU - Dubin, Celina

AU - Dahabreh, Dante

AU - Han, Joseph

AU - Del Duca, Ester

AU - Estrada, Yeriel D.

AU - Zhang, Ning

AU - Kimmel, Grace W.

AU - Singer, Giselle

AU - Krueger, James G.

AU - Pavel, Ana B.

AU - Guttman-Yassky, Emma

N1 - Funding Information: We acknowledge the Department of Dermatology at the Icahn School of Medicine for its contribution to this study. Publisher Copyright: © 2021 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.

PY - 2021/10

Y1 - 2021/10

N2 - Background: Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity. Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT). Results: A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp (p <.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (p <.05). AA scalp demonstrated significantly greater biomarker dysregulation compared to blood. An integrated multivariate approach combining scalp and serum biomarkers improved correlations with disease severity/SALT. Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.

AB - Background: Alopecia areata (AA) is characterized by immune dysregulation in both scalp and blood, but a large-scale approach establishing biomarkers of AA incorporating both scalp tissue and serum compartments is lacking. We aimed to characterize the transcriptomic signature of AA lesional and nonlesional scalp compared to healthy scalp and determine its relationship with the blood proteome in the same individuals, with comparative correlations to clinical AA disease severity. Methods: We evaluated lesional and nonlesional scalp tissues and serum from patients with moderate-to-severe AA (n = 18) and healthy individuals (n = 8). We assessed 33,118 genes in AA scalp tissue using RNAseq transcriptomic evaluation and 340 inflammatory proteins in serum using OLINK high-throughput proteomics. Univariate and multivariate approaches were used to correlate disease biomarkers with Severity of Alopecia Tool (SALT). Results: A total of 608 inflammatory genes were differentially expressed in lesional AA scalp (fold change/FCH>1.5, false discovery rate/FDR<0.05) including Th1 (IFNG/IL12B/CXCL11), Th2 (IL13/CCL18), and T-cell activation-related (ICOS) products. Th1/Th2-related markers were significantly correlated with AA clinical severity in lesional/nonlesional tissue, while keratins (KRT35/KRT83/KRT81) were significantly downregulated in lesional compared to healthy scalp (p <.05). Expression of cardiovascular/atherosclerosis-related markers (MMP9/CCL2/IL1RL1/IL33R/ST2/AGER) in lesional scalp correlated with their corresponding serum expression (p <.05). AA scalp demonstrated significantly greater biomarker dysregulation compared to blood. An integrated multivariate approach combining scalp and serum biomarkers improved correlations with disease severity/SALT. Conclusion: This study contributes a unique understanding of the phenotype of moderate-to-severe AA with an integrated scalp and serum biomarker model suggesting the systemic nature of the disease, advocating for the need for immune-based systemic treatment.

KW - OLINK

KW - RNAseq

KW - alopecia areata

KW - bioinformatics

KW - biomarkers

UR - http://www.scopus.com/inward/record.url?scp=85107990647&partnerID=8YFLogxK

U2 - 10.1111/all.14814

DO - 10.1111/all.14814

M3 - Article

C2 - 33721346

AN - SCOPUS:85107990647

SN - 0105-4538

VL - 76

SP - 3053

EP - 3065

JO - Allergy: European Journal of Allergy and Clinical Immunology

JF - Allergy: European Journal of Allergy and Clinical Immunology

IS - 10

ER -

An integrated scalp and blood biomarker approach suggests the systemic nature of alopecia areata

Abstract

Keywords

Access to Document

Fingerprint

Cite this