Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Jan 6:13:1054119.
doi: 10.3389/fimmu.2022.1054119. eCollection 2022.

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

Zihan Dong  1   2 , Åsne Myklebust  3   4 , Ingvild Bjellmo Johnsen  4 , Tuomas Jartti  5   6   7 , Henrik Døllner  3   4 , Kari Risnes  3   4 , Andrew T DeWan  2   8
Affiliations

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

Zihan Dong et al. Front Immunol. .

Abstract

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.

Keywords: bronchiolitis; childhood asthma; gene-environment interaction (G × E); genetic risk factors; type 2 cytokines; viral respiratory infection.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Similar articles

See all similar articles

Cited by

References

    1. Soumelis V, Reche PA, Kanzler H, Yuan W, Edward G, Homey B, et al. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat Immunol (2002) 3(7):673–80. doi: 10.1038/ni805 - DOI - PubMed
    1. Lukkarinen M, Koistinen A, Turunen R, Lehtinen P, Vuorinen T, Jartti T. Rhinovirus-induced first wheezing episode predicts atopic but not nonatopic asthma at school age. J Allergy Clin Immunol (2017) 140(4):988–95. doi: 10.1016/j.jaci.2016.12.991 - DOI - PMC - PubMed
    1. Jackson DJ, Gangnon RE, Evans MD, Roberg KA, Anderson EL, Pappas TE, et al. Wheezing rhinovirus illnesses in early life predict asthma development in high-risk children. Am J Respir Crit Care Med (2008) 178(7):667–72. doi: 10.1164/rccm.200802-309OC - DOI - PMC - PubMed
    1. Makrinioti H, Hasegawa K, Lakoumentas J, Xepapadaki P, Tsolia M, Castro-Rodriguez JA, et al. The role of respiratory syncytial virus- and rhinovirus-induced bronchiolitis in recurrent wheeze and asthma-a systematic review and meta-analysis. Pediatr Allergy Immunol (2022) 33(3):e13741. doi: 10.1111/pai.13741 - DOI - PubMed
    1. Corren J, Pham T-H, Gil EG, Sałapa K, Ren P, Parnes JR, et al. Baseline type 2 biomarker levels and response to tezepelumab in severe asthma. Allergy (2021) 77(6):1786-96. doi: 10.1111/all.15197 - DOI - PMC - PubMed

Publication types