Scalp and serum profiling of frontal fibrosing alopecia reveals scalp immune and fibrosis dysregulation with no systemic involvement

Celina Dubin, Jacob W. Glickman, Ester Del Duca, Sumanth Chennareddy, Joseph Han, Dante Dahabreh, Yeriel D. Estrada, Ning Zhang, Grace W. Kimmel, Giselle Singer, Mashkura Chowdhury, Andrew Y. Zheng, Michael Angelov, Jesús Gay-Mimbrera, Juan Ruano Ruiz, James G. Krueger, Ana B. Pavel, Emma Guttman-Yassky

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Background: Frontal fibrosing alopecia (FFA) is a progressive, scarring alopecia of the frontotemporal scalp that poses a substantial burden on quality of life. Large-scale global profiling of FFA is lacking, preventing the development of effective therapeutics. Objective: To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity. Methods: This cross-sectional study assessed 33,118 genes in scalp using RNA sequencing and 350 proteins in serum using OLINK high-throughput proteomics. Disease biomarkers were also correlated with clinical severity and a fibrosis gene set. Results: Genes differentially expressed in lesional FFA included markers related to Th1 (IFNγ/CXCL9/CXCL10), T-cell activation (CD2/CD3/CCL19/ICOS), fibrosis (CXCR3/FGF14/FGF22/VIM/FN1), T-regulatory (FOXP3/TGFB1/TGFB3), and Janus kinase/JAK (JAK3/STAT1/STAT4) (Fold changes [FCH]>1.5, FDR<.05 for all). Only one protein, ADM, was differentially expressed in FFA serum compared to normal (FCH>1.3, FDR<.05). Significant correlations were found between scalp biomarkers (IL-36RN/IL-25) and FFA severity, as well as between JAK/STAT and fibrosis gene-sets (r>.6; P <.05). Limitations: This study was limited by a small sample size and predominantly female FFA patients. Conclusion: Our data characterize FFA as an inflammatory condition limited to scalp, involving Th1/JAK skewing, with associated fibrosis and elevated T-regulatory markers, suggesting the potential for disease reversibility with JAK/STAT inhibition.

Original languageEnglish
Pages (from-to)551-562
Number of pages12
JournalJournal of the American Academy of Dermatology
Volume86
Issue number3
DOIs
StatePublished - Mar 2022

Keywords

  • JAK/STAT
  • OLINK
  • Th1
  • alopecia areata
  • biomarkers
  • frontal fibrosing alopecia
  • hair keratins
  • proteomics

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