Early-life microRNA signatures in cord blood associated with allergic rhinitis and asthma development

Hooman Mirzakhani; Alberta L Wang; Rinku Sharma; Maoyun Sun; Ronald Panganiban; Quan Lu; Michael McGeachie; Zheng Lu; Augusto A Litonjua; Kelan G Tantisira; Scott T Weiss

doi:10.1016/j.jaci.2024.12.1077

Early-life microRNA signatures in cord blood associated with allergic rhinitis and asthma development

J Allergy Clin Immunol. 2024 Dec 24:S0091-6749(24)02410-2. doi: 10.1016/j.jaci.2024.12.1077. Online ahead of print.

Authors

Affiliations

¹ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: hoomi@post.harvard.edu.
² Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: awang@bwh.harvard.edu.
³ Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA, USA.
⁴ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
⁶ Division of Pediatric Pulmonology, University of Rochester Medical Center, Rochester, NY, USA.
⁷ Division of Respiratory Medicine, Rady Children's Hospital-San Diego, San Diego, CA, USA.

PMID: 39724972
DOI: 10.1016/j.jaci.2024.12.1077

Abstract

Background: MicroRNAs (miRNAs) are involved in the biological regulation of asthma and allergies.

Objectives: To investigate the association between cord blood miRNAs and the development of allergic rhinitis and early childhood asthma.

Methods: miRNAs were sequenced from cord blood of subjects participating in the Vitamin D Antenatal Asthma Reduction Trial. Multivariable miRNA differential expression analyses were performed to examine their association with physician diagnosed asthma and allergic rhinitis by age 3, as well as active asthma status at age 6 years. miRNA signatures were further investigated for their ability to induce human airway smooth muscle cell (HASMC) proliferation in vitro.

Results: In a cohort of 389 subjects, elevated cord blood expression of miR-149-5p was associated with both age 3 allergic rhinitis and asthma (log₂FC: 1.87 and 1.42, respectively, FDR<0.001), as well as age 6 active asthma status (log₂FC: 2.26, FDR<0.001). Higher expressions of miR-99b-5p, miR-125a-5p, and miR-200c-3p were also associated with both diagnosis of allergic rhinitis at age of 3 years and active asthma status at age of 6 (allergic rhinitis: log₂FC: 0.6, 0.62, and 1.06, respectively, FDR<0.001; active asthma: log₂FC: 0.55, 0.60, 1.10, respectively, FDR<0.001, respectively). Higher expression of miR-145-5p was associated with both new onset asthma after age 3 and active asthma status at age 6 (log₂FC: 0.73 and 0.40, FDR<0.001, respectively). These five miRNA signatures target key hubs in the interactome module of 71 genes associated with allergic rhinitis and asthma. Transfection of miR-125a-5p and miR-145-5p into HASMC induced cell proliferation.

Conclusion: The dysregulation of cord blood miRNAs at birth are associated with allergic rhinitis and early childhood asthma. The miRNAs that regulate post-embryonic development and immune response may serve as potential biomarkers and preventive targets for asthma.

Keywords: allergic rhinitis; asthma; child; cord blood; interactome; microRNA.