Ichthyosis molecular fingerprinting shows profound T
Adolescent
Adult
Aged
Child
DNA Fingerprinting
Female
Filaggrin Proteins
Genome
Humans
Ichthyosis
/ genetics
Interleukin-1
/ genetics
Interleukin-17
/ genetics
Lipid Metabolism
/ genetics
Lymphocyte Activation
Male
Microarray Analysis
Middle Aged
Netherton Syndrome
/ genetics
T-Lymphocytes
/ immunology
Th17 Cells
/ immunology
Tight Junctions
/ genetics
Transcriptome
Young Adult
IL-17
IL-36
Netherton syndrome
Psoriasis
TNF-α
atopic dermatitis
congenital ichthyosiform erythroderma
epidermal barrier
epidermolytic ichthyosis
immune
inflammation
lamellar ichthyosis
precision medicine
targeted therapy
Journal
The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002
Informations de publication
Date de publication:
02 2019
02 2019
Historique:
received:
01
01
2018
revised:
23
02
2018
accepted:
21
03
2018
pubmed:
29
5
2018
medline:
18
2
2020
entrez:
28
5
2018
Statut:
ppublish
Résumé
Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy. We sought to profile the molecular fingerprint of the most common orphan ichthyoses. Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16). Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.
Sections du résumé
BACKGROUND
Ichthyoses are a group of rare skin disorders lacking effective treatments. Although genetic mutations are progressively delineated, comprehensive molecular phenotyping of ichthyotic skin could suggest much-needed pathogenesis-based therapy.
OBJECTIVE
We sought to profile the molecular fingerprint of the most common orphan ichthyoses.
METHODS
Gene, protein, and serum studies were performed on skin and blood samples from 29 patients (congenital ichthyosiform erythroderma, n = 9; lamellar ichthyosis, n = 8; epidermolytic ichthyosis, n = 8; and Netherton syndrome, n = 4), as well as age-matched healthy control subjects (n = 14), patients with psoriasis (n = 30), and patients with atopic dermatitis (AD; n = 16).
RESULTS
Using criteria of a fold change of greater than 2 and a false discovery rate of less than 0.05, 132 differentially expressed genes were shared commonly among all ichthyoses, including many IL-17 and TNF-α-coregulated genes, which are considered hallmarks of psoriasis (defensin beta 4A, kynureninase, and vanin 3). Although striking upregulation of TH17 pathway genes (IL17F and IL36B/G) resembling that seen in patients with psoriasis was common to all patients with ichthyoses in a severity-related manner, patients with Netherton syndrome showed the greatest T-cell activation (inducible costimulator [ICOS]) and a broader immune phenotype with T
CONCLUSION
Similar to patients with AD and psoriasis, in whom cytokine dysregulation and barrier impairment orchestrate disease phenotypes, psoriasis-like immune dysregulation and lipid alterations characterize the ichthyoses. These data support the testing of IL-17/IL-36-targeted therapeutics for patients with ichthyosis similar to those used in patients with psoriasis.
Identifiants
pubmed: 29803800
pii: S0091-6749(18)30759-0
doi: 10.1016/j.jaci.2018.03.021
pmc: PMC7195861
mid: NIHMS1057361
pii:
doi:
Substances chimiques
FLG protein, human
0
Filaggrin Proteins
0
Interleukin-1
0
Interleukin-17
0
interleukin 36, human
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
604-618Subventions
Organisme : NIAMS NIH HHS
ID : P30 AR057216
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR068392
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Informations de copyright
Copyright © 2018 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.
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