Scalp and serum profiling of frontal fibrosing alopecia reveals scalp immune and fibrosis dysregulation with no systemic involvement.
JAK/STAT
OLINK
Th1
alopecia areata
biomarkers
frontal fibrosing alopecia
hair keratins
proteomics
Journal
Journal of the American Academy of Dermatology
ISSN: 1097-6787
Titre abrégé: J Am Acad Dermatol
Pays: United States
ID NLM: 7907132
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
02
04
2021
accepted:
11
05
2021
pubmed:
28
5
2021
medline:
15
4
2022
entrez:
27
5
2021
Statut:
ppublish
Résumé
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. To characterize FFA compared to normal and alopecia areata using broad molecular profiling and to identify biomarkers linked to disease severity. 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. 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). This study was limited by a small sample size and predominantly female FFA patients. 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.
Sections du résumé
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.
Identifiants
pubmed: 34044102
pii: S0190-9622(21)00999-3
doi: 10.1016/j.jaad.2021.05.016
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
551-562Informations de copyright
Copyright © 2021 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of interest Dr Guttman-Yassky is an employee of Mount Sinai and has received research funds (grants paid to the institution) from Abbvie, Almirall, AnaptysBio, Asana Biosciences, Boerhinger-Ingelhiem, Dermavant, DS Biopharma, Eli Lilly, Ichnos Sciences, Innovaderm, Janssen, Kiniska, Kyowa Kirin, Leo Pharma, Novan, Pfizer, Ralexar, Regeneron Pharmaceuticals, Inc, Sienna Biopharma, UCB, and Union Therapeutics, and is a consultant for Abbvie, Aditum Bio, Almirall, Amgen, Asana Biosciences, AstraZeneca, Boerhinger-Ingelhiem, Cara Therapeutics, Celgene, Concert, DBV, Dermira, DS Biopharma, Eli Lilly, EMD Serono, Escalier, Galderma, Ichnos Sciences, Incyte Kyowa Kirin, Leo Pharma, Mitsubishi Tanabe, Pandion Therapeutics, Pfizer, RAPT Therapeutics, Regeneron Pharmaceuticals, Inc, Sanofi, Sienna Biopharma, Target PharmaSolutions and Union Therapeutics. Dr Krueger is an employee of Rockefeller University and has received research funds (grants paid to the institution) from Novartis, Pfizer, Amgen, Eli Lilly, Boehringer, Innovaderm, BMS, Janssen, Abbvie, Paraxel, Leo Pharma, Vitae, Akros, Regeneron, Allergan, Novan, Biogen MA, Sienna, UCB, Celgene, Botanix, Incyte, Avillion, and Exicure, and is a consultant for Novartis, Pfizer, Amgen, Eli Lilly, Boehringer, BiogenIdec, Abbvie, Leo Pharma, Escalier, Valeant, Aurigne, Allergan, Asana, UCB, Sienna, Celgene, Nimbus, Menlo, Aristea, Sanofi, Sun Pharma, Almirall, Arena, BMS, Ventyx, Aclaris, Galapagos. The remaining authors have no conflicts to disclose.