Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways

Authors

David Martino, Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Nikki Schultz, Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Ravinder Kaur, Rochester Regional HealthFollow
Simon D. van Haren, Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA.
Nina Kresoje, Wal-Yan Respiratory Research Centre, Telethon Kids Institute, University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Annmarie Hoch, Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA.
Joann Diray-Arce, Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA.
Jessica Lasky Su, Channing Division of Network Medicine and Harvard Medical School, Boston, MA, 02115, USA.
Ofer Levy, Precision Vaccines Program, Department of Pediatrics, Boston Children's Hospital, 300 Longwood Ave, BCH 3104, Boston, MA, 02115, USA.
Michael Pichichero, Rochester Regional HealthFollow

Department

Research

Document Type

Article

Publication Title

Clinical Epigenetics

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).

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.

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.

First Page

85

DOI

10.1186/s13148-024-01703-0

Volume

16

Issue

1

Publication Date

7-3-2024

Medical Subject Headings

Humans; Asthma (genetics, immunology); Leukocytes, Mononuclear (immunology, metabolism); DNA Methylation (genetics); Male; Female; Respiratory Tract Infections (immunology, genetics); Infant; Epigenesis, Genetic (genetics); Polymorphism, Single Nucleotide; CpG Islands (genetics); Retrospective Studies; Genome-Wide Association Study (methods); Child, Preschool; Child; Proof of Concept Study

PubMed ID

38961479

Recommended Citation

Martino, D., Schultz, N., Kaur, R., van Haren, S. D., Kresoje, N., Hoch, A., Diray-Arce, J., Su, J. L., Levy, O., & Pichichero, M. (2024). Respiratory infection- and asthma-prone, low vaccine responder children demonstrate distinct mononuclear cell DNA methylation pathways. Clinical Epigenetics, 16 (1), 85. https://doi.org/10.1186/s13148-024-01703-0