Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways

The primary forms of cicatricial (scarring) alopecia (PCA) are a group of inflammatory, irreversible hair loss disorders characterized by immune cell infiltrates targeting hair follicles (HFs). Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and centrifugal cicatricial alopecia (CCCA) a...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Eddy H C, Monga, Isha, Sallee, Brigitte N, Chen, James C, Abdelaziz, Alexa R, Perez-Lorenzo, Rolando, Bordone, Lindsey A, Christiano, Angela M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308563/
https://www.ncbi.nlm.nih.gov/pubmed/35899069
http://dx.doi.org/10.1093/pnasnexus/pgac111
_version_ 1784753009232707584
author Wang, Eddy H C
Monga, Isha
Sallee, Brigitte N
Chen, James C
Abdelaziz, Alexa R
Perez-Lorenzo, Rolando
Bordone, Lindsey A
Christiano, Angela M
author_facet Wang, Eddy H C
Monga, Isha
Sallee, Brigitte N
Chen, James C
Abdelaziz, Alexa R
Perez-Lorenzo, Rolando
Bordone, Lindsey A
Christiano, Angela M
author_sort Wang, Eddy H C
collection PubMed
description The primary forms of cicatricial (scarring) alopecia (PCA) are a group of inflammatory, irreversible hair loss disorders characterized by immune cell infiltrates targeting hair follicles (HFs). Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and centrifugal cicatricial alopecia (CCCA) are among the main subtypes of PCAs. The pathogenesis of the different types of PCAs are poorly understood, and current treatment regimens yield inconsistent and unsatisfactory results. We performed high-throughput RNA-sequencing on scalp biopsies of a large cohort PCA patients to develop gene expression-based signatures, trained into machine-learning-based predictive models and pathways associated with dysregulated gene expression. We performed morphological and cytokine analysis to define the immune cell populations found in PCA subtypes. We identified a common PCA gene signature that was shared between LPP, FFA, and CCCA, which revealed a significant over-representation of mast cell (MC) genes, as well as downregulation of cholesterogenic pathways and upregulation of fibrosis and immune signaling genes. Immunohistological analyses revealed an increased presence of MCs in PCAs lesions. Our gene expression analyses revealed common pathways associated with PCAs, with a strong association with MCs. The indistinguishable differences in gene expression profiles and immune cell signatures between LPP, FFA, and CCCA suggest that similar treatment regimens may be effective in treating these irreversible forms of hair loss.
format Online
Article
Text
id pubmed-9308563
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Oxford University Press
record_format MEDLINE/PubMed
spelling pubmed-93085632022-07-25 Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways Wang, Eddy H C Monga, Isha Sallee, Brigitte N Chen, James C Abdelaziz, Alexa R Perez-Lorenzo, Rolando Bordone, Lindsey A Christiano, Angela M PNAS Nexus Biological, Health, and Medical Sciences The primary forms of cicatricial (scarring) alopecia (PCA) are a group of inflammatory, irreversible hair loss disorders characterized by immune cell infiltrates targeting hair follicles (HFs). Lichen planopilaris (LPP), frontal fibrosing alopecia (FFA), and centrifugal cicatricial alopecia (CCCA) are among the main subtypes of PCAs. The pathogenesis of the different types of PCAs are poorly understood, and current treatment regimens yield inconsistent and unsatisfactory results. We performed high-throughput RNA-sequencing on scalp biopsies of a large cohort PCA patients to develop gene expression-based signatures, trained into machine-learning-based predictive models and pathways associated with dysregulated gene expression. We performed morphological and cytokine analysis to define the immune cell populations found in PCA subtypes. We identified a common PCA gene signature that was shared between LPP, FFA, and CCCA, which revealed a significant over-representation of mast cell (MC) genes, as well as downregulation of cholesterogenic pathways and upregulation of fibrosis and immune signaling genes. Immunohistological analyses revealed an increased presence of MCs in PCAs lesions. Our gene expression analyses revealed common pathways associated with PCAs, with a strong association with MCs. The indistinguishable differences in gene expression profiles and immune cell signatures between LPP, FFA, and CCCA suggest that similar treatment regimens may be effective in treating these irreversible forms of hair loss. Oxford University Press 2022-07-11 /pmc/articles/PMC9308563/ /pubmed/35899069 http://dx.doi.org/10.1093/pnasnexus/pgac111 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Biological, Health, and Medical Sciences
Wang, Eddy H C
Monga, Isha
Sallee, Brigitte N
Chen, James C
Abdelaziz, Alexa R
Perez-Lorenzo, Rolando
Bordone, Lindsey A
Christiano, Angela M
Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title_full Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title_fullStr Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title_full_unstemmed Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title_short Primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
title_sort primary cicatricial alopecias are characterized by dysregulation of shared gene expression pathways
topic Biological, Health, and Medical Sciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9308563/
https://www.ncbi.nlm.nih.gov/pubmed/35899069
http://dx.doi.org/10.1093/pnasnexus/pgac111
work_keys_str_mv AT wangeddyhc primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT mongaisha primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT salleebrigitten primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT chenjamesc primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT abdelazizalexar primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT perezlorenzorolando primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT bordonelindseya primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways
AT christianoangelam primarycicatricialalopeciasarecharacterizedbydysregulationofsharedgeneexpressionpathways