DNA methylation patterns in juvenile systemic sclerosis and localized scleroderma.
Epigenetics
Juvenile-onset scleroderma
Localized scleroderma
Methylation
Systemic sclerosis
Journal
Clinical immunology (Orlando, Fla.)
ISSN: 1521-7035
Titre abrégé: Clin Immunol
Pays: United States
ID NLM: 100883537
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
19
04
2021
revised:
12
05
2021
accepted:
12
05
2021
pubmed:
17
5
2021
medline:
17
8
2021
entrez:
16
5
2021
Statut:
ppublish
Résumé
Scleroderma refers to a group of chronic fibrotic immune-mediated diseases of unknown etiology. Characterizing epigenetic changes in childhood-onset scleroderma, systemic sclerosis or localized scleroderma, has not been previously performed. The aim of this study was to assess DNA methylation differences and similarities between juvenile systemic sclerosis (jSSc) and juvenile localized scleroderma (jLS) compared to matched healthy controls. Genome-wide DNA methylation changes in peripheral blood mononuclear cell samples were assessed using the MethylationEPIC array followed by bioinformatic analysis and limited functional assessment. We identified a total of 105 and 144 differentially methylated sites compared to healthy controls in jSSc and jLS, respectively. The majority of differentially methylated sites and genes represented were unique to either jSSc or jLS suggesting a different underlying epigenetic pattern in both diseases. Among shared differentially methylated genes, methylation levels in a CpG site in FGFR2 can distinguish between LS and healthy PBMCs with a high accuracy. Canonical pathway analysis revealed that inflammatory pathways were enriched in genes differentially methylated in jSSc, including STAT3, NF-κB, and IL-15 pathways. In contrast, the HIPPO signaling pathway was enriched in jLS. Our data also suggest a potential role for NOTCH3 in both jSSc and jLS, and revealed a number of transcription factors unique to each of the two diseases. In summary, our data revealed important insights into jSSc and jLS and suggest a potentially novel epigenetic diagnostic biomarker for LS.
Identifiants
pubmed: 33992755
pii: S1521-6616(21)00093-0
doi: 10.1016/j.clim.2021.108756
pmc: PMC8206011
mid: NIHMS1704482
pii:
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
108756Subventions
Organisme : NIAID NIH HHS
ID : R01 AI097134
Pays : United States
Informations de copyright
Copyright © 2021 Elsevier Inc. All rights reserved.
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