University of Oulu

Dong Z, Myklebust Å, Johnsen IB, Jartti T, Døllner H, Risnes K and DeWan AT (2023) Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood. Front. Immunol. 13:1054119. doi: 10.3389/fimmu.2022.1054119

Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood

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Author: Dong, Zihan1,2; Myklebust, Åsne3,4; Johnsen, Ingvild Bjellmo4;
Organizations: 1Department of Biostatistics, Yale School of Public Health, New Haven, CT, United States
2Center for Perinatal, Pediatric and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, United States
3Children’s Clinic, St Olav Hospital, University Hospital, Trondheim, Norway
4Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
5PEDEGO Research Unit, University of Oulu, Oulu, Finland
6Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, Oulu, Finland
7Department of Pediatrics and Adolescent Medicine, Turku University Hospital and University of Turku, Turku, Finland
8Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, United States
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.6 MB)
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Language: English
Published: Frontiers Media, 2023
Publish Date: 2023-07-07


Background: Genome-wide association studies of asthma have identified associations with variants in type-2 related genes. Also, specific interactions between genetic variants and viral bronchiolitis in the development of asthma has been suggested.

Objective: To conduct a gene-based analysis of genetic variants in type 2 cytokine related genes as risk factors for allergic asthma at school age, and further, to study their interaction with specific viral infections in early childhood.

Methods: A prospectively investigated cohort of children with previous bronchiolitis and controls came for follow-up at school age. The research visit, blinded to viral exposure, included detailed lung function tests, laboratory investigation, and questionnaires. Allergic asthma was defined as typical symptoms plus objective variable airway obstruction, in addition to laboratory verified atopy (elevated eosinophil count or sensitization to an allergen). Targeted and complete sequencing was performed for nine type 2 cytokine candidate genes: IL4, 5, 13, 25, 33 and 37, IL17RB, CRLF2 and TSLP.

Results: At follow-up, there were 109 children with genetic data, 91 with a history of bronchiolitis (46% respiratory syncytial virus, 24% human rhinovirus, 15% human metapneumovirus and 14% mixed viral etiology) and 18 without. The median age was 9.4 years (range 6–13) and 41 (38%) had laboratory verified atopy. Twenty-one children (19%) met the definition of allergic asthma. After adjusting for age, sex and five viral categories, IL33 achieved nominal significance (p = 0.017) for a positive association with allergic asthma development. In the gene-virus interaction analysis, the variant set in IL17RB demonstrated a nominally significant positive interaction with human metapneumovirus infection (p=0.05).

Conclusion: The results highlight the multifactorial nature of allergic asthma risk, with both viral infection and inherited genetic variants contributing to increasing risk. Results for IL33 and IL17RB were nominally significant and are potential candidate targets for designing therapeutics and early screening, but these results must be replicated in an independent study.

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Series: Frontiers in immunology
ISSN: 1664-3224
ISSN-E: 1664-3224
ISSN-L: 1664-3224
Volume: 13
Article number: 1054119
DOI: 10.3389/fimmu.2022.1054119
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
3123 Gynaecology and paediatrics
3121 General medicine, internal medicine and other clinical medicine
Funding: Liaison Committee for Education, Research, and Innovation in Central Norway (Samarbeidsorganet); The Faculty of Medicine and Health Sciences, NTNU and Children’s Clinic, St Olav University Hospital.
Copyright information: © 2023 Dong, Myklebust, Johnsen, Jartti, Døllner, Risnes and DeWan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.