Altered DNA methylation and gene expression predict disease severity in patients with Aicardi-Goutières syndrome.
Clin Immunol
; 249: 109299, 2023 04.
Article
em En
| MEDLINE
| ID: mdl-36963449
ABSTRACT
Aicardi-Goutières Syndrome (AGS) is a rare neuro-inflammatory disease characterized by increased expression of interferon-stimulated genes (ISGs). Disease-causing mutations are present in genes associated with innate antiviral responses. Disease presentation and severity vary, even between patients with identical mutations from the same family. This study investigated DNA methylation signatures in PBMCs to understand phenotypic heterogeneity in AGS patients with mutations in RNASEH2B. AGS patients presented hypomethylation of ISGs and differential methylation patterns (DMPs) in genes involved in "neutrophil and platelet activation". Patients with "mild" phenotypes exhibited DMPs in genes involved in "DNA damage and repair", whereas patients with "severe" phenotypes had DMPs in "cell fate commitment" and "organ development" associated genes. DMPs in two ISGs (IFI44L, RSAD2) associated with increased gene expression in patients with "severe" when compared to "mild" phenotypes. In conclusion, altered DNA methylation and ISG expression as biomarkers and potential future treatment targets in AGS.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Autoimunes do Sistema Nervoso
/
Malformações do Sistema Nervoso
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Idioma:
En
Revista:
Clin Immunol
Assunto da revista:
ALERGIA E IMUNOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Itália