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Illi, S. ; Depner, M. ; Pfefferle, P.I.* ; Renz, H.* ; Roduit, C.* ; Taft, D.H.* ; Kalanetra, K.M.* ; Mills, D.A.* ; Farquharson, F.M.* ; Louis, P.* ; Schmaußer-Hechfellner, E. ; Divaret-Chauveau, A.* ; Lauener, R.* ; Karvonen, A.M.* ; Pekkanen, J.* ; Kirjavainen, P.V.* ; Roponen, M.* ; Riedler, J.* ; Kabesch, M.* ; Schaub, B.* ; von Mutius, E.

Immune responsiveness to LPS determines risk of childhood wheeze and asthma in 17q21 risk allele carriers.

Am. J. Respir. Crit. Care Med. 205, 641-650 (2022)
DOI
Free by publisher: Publ. Version/Full Text online available 01/2023 Open Access Green: Postprint online available 01/2023
BACKGROUND: In murine models microbial exposures induce protection from experimental allergic asthma through innate immunity. Our aim was to assess the association of early life innate immunity with the development of asthma in children at risk. METHODS: In the PASTURE farm birth cohort innate, Th2, Th1 and Th17 cytokine expression at age 1 year was measured after stimulation of PBMCs with lipopolysaccharide (LPS) in N=445 children. Children at risk of asthma were defined based on single-nucleotide polymorphisms at the 17q21 asthma gene locus. Specifically, we used the SNP rs7216389 in the GSDMB gene. Wheeze in the 1st year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. RESULTS: Not all cytokines were detectable in all children after LPS-stimulation. When classifying detectability of cytokines by latent class analysis, carrying the 17q21 risk allele rs7216389 was associated with risk of wheeze only in the class with the lowest level of LPS-induced activation, odds ratio (OR)=1.89, 95%-CI 1.13-3.16, p=0.015. In contrast, in children with high cytokine activation after LPS-stimulation no association of the 17q21 risk allele with wheeze (OR=0.63, 95%-CI 0.29-1.40, p=0.258, p=0.034 for interaction) or school age asthma was observed. In these children consumption of unprocessed cow's milk was associated with higher cytokine activation (OR=3.37, 95%-CI 1.56-7.30, p=0.002), which was in part mediated by the gut microbiome. CONCLUSIONS: These findings suggest that within the 17q21 genotype asthma risk can be mitigated by activated immune responses after innate stimulation, which is partly mediated by a gut-immune axis.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Innate Immune Response, Children, 17q21 Genotype, Farm Environment, Unprocessed Cow’s Milk, Gut Microbiome
ISSN (print) / ISBN 1073-449X
e-ISSN 1535-4970
Quellenangaben Volume: 205, Issue: 6, Pages: 641-650 Article Number: , Supplement: ,
Publisher American Thoracic Society
Reviewing status Peer reviewed
Institute(s) Institute of Asthma and Allergy Prevention (IAP)