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Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways.
- Source :
-
Clinical epigenetics [Clin Epigenetics] 2024 Jul 03; Vol. 16 (1), pp. 85. Date of Electronic Publication: 2024 Jul 03. - Publication Year :
- 2024
-
Abstract
- Background: Infants with frequent viral and bacterial respiratory infections exhibit compromised immunity to routine immunizations. They are also more likely to develop chronic respiratory diseases in later childhood. This study investigated the feasibility of epigenetic profiling to reveal endotype-specific molecular pathways with potential for early identification and immuno-modulation. Peripheral blood mononuclear cells from respiratory infection allergy/asthma-prone (IAP) infants and non-infection allergy/asthma prone (NIAP) were retrospectively selected for genome-wide DNA methylation and single nucleotide polymorphism analysis. The IAP infants were enriched for the low vaccine responsiveness (LVR) phenotype (Fisher's exact p-value = 0.02).<br />Results: An endotype signature of 813 differentially methylated regions (DMRs) comprising 238 lead CpG associations (FDR < 0.05) emerged, implicating pathways related to asthma, mucin production, antigen presentation and inflammasome activation. Allelic variation explained only a minor portion of this signature. Stimulation of mononuclear cells with monophosphoryl lipid A (MPL), a TLR agonist, partially reversed this signature at a subset of CpGs, suggesting the potential for epigenetic remodeling.<br />Conclusions: This proof-of-concept study establishes a foundation for precision endotyping of IAP children and highlights the potential for immune modulation strategies using adjuvants for future investigation.<br /> (© 2024. The Author(s).)
- Subjects :
- Humans
Male
Female
Infant
Polymorphism, Single Nucleotide
CpG Islands genetics
Retrospective Studies
Genome-Wide Association Study methods
Child, Preschool
Child
Proof of Concept Study
Asthma genetics
Asthma immunology
Leukocytes, Mononuclear immunology
Leukocytes, Mononuclear metabolism
DNA Methylation genetics
Respiratory Tract Infections immunology
Respiratory Tract Infections genetics
Epigenesis, Genetic genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1868-7083
- Volume :
- 16
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Clinical epigenetics
- Publication Type :
- Academic Journal
- Accession number :
- 38961479
- Full Text :
- https://doi.org/10.1186/s13148-024-01703-0