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 journalArticlepeer-review

9 Scopus citations


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 languageEnglish
Pages (from-to)3053-3065
Number of pages13
JournalAllergy: European Journal of Allergy and Clinical Immunology
Issue number10
StatePublished - Oct 2021


  • RNAseq
  • alopecia areata
  • bioinformatics
  • biomarkers


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