Scalp and serum profiling of frontal fibrosing alopecia reveals scalp immune and fibrosis dysregulation with no systemic involvement - 30/06/21
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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.
Le texte complet de cet article est disponible en PDF.Key words : alopecia areata, biomarkers, frontal fibrosing alopecia, JAK/STAT, hair keratins, OLINK, proteomics, Th1
Abbreviations used : AA, AD, CCL, DEG, ECM, FFA, FFASI, FCH, JAK, IFN, IL, LPP, SALT
Plan
Funding sources: None. |
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C Dubin and JW Glickman contributed equally to this article. |
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IRB approval status: Reviewed and approved by the Department of Dermatology at the Icahn School of Medicine; approval protocol HS# GCO 14-0863. |
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Reprints not available from the authors. |
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