Abstract
Background: Asthma and allergies are complex diseases caused by gene-environment interplay. Human β-defensin 2 (hBD-2) is a host defense peptide secreted by epithelial cells with immunomodulatory effects and which was shown to improve asthma and IBD in mice.
Objectives: We hypothesized that adequate hBD-2 production is crucial for prevention of asthma and allergy and that hBD-2 coding genes (DEFB4A and -B) variants could play a role in disease development.
Methods: Single nucleotide polymorphisms (SNPs) were genotyped by MALDI-TOF MS (n=13) in 1,238 children living in rural areas from the GABRIELA Ulm cohort. Restriction assays and Sanger sequencing were performed to identify mutations, SNPs and copy number variations in DEFB4A and -B loci. To explore its prophylactic potential, mimicking a protective farm setting, we administered hBD-2 orally in mice with house dust mite (HDM)-induced asthma prior to allergy challenge.
Results: Six asthma and atopy-associated DEFB4A and -B gene variants were detected with rs543538872 (p=2.42*10-90) being the top asthma hit. Polymorphism rs62640720 was associated with asthma, atopy, atopic asthma, and non-atopic asthma. Lack of DEFB4A was associated with allergy only (p=0.012). Prophylactic oral application of hBD-2 significantly reduced lung resistance and pulmonary inflammation in HDM-exposed mice.
Conclusions: Variations in hBD-2 coding genes associate with increased asthma and allergy risk, while early hBD-2 administration hinders atopic asthma symptoms in mice. Further research is needed to evaluate if and how hBD-2 is involved in the protective farm effect against asthma and allergy.
Footnotes
Cite this article as: European Respiratory Journal 2021; 58: Suppl. 65, OA1620.
This abstract was presented at the 2021 ERS International Congress, in session “Prediction of exacerbations in patients with COPD”.
This is an ERS International Congress abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2021