Illi, Sabina and Depner, Martin and Pfefferle, Petra Ina and Renz, Harald and Roduit, Caroline and Taft, Diana Hazard and Kalanetra, Karen M. and Mills, David A. and Farquharson, Freda M. and Louis, Petra and Schmausser-Hechfellner, Elisabeth and Divaret-Chauveau, Amandine and Lauener, Roger and Karvonen, Anne M. and Pekkanen, Juha and Kirjavainen, Pirkka and Roponen, Marjut and Riedler, Josef and Kabesch, Michael and Schaub, Bianca and von Mutius, Erika (2022) Immune Responsiveness to LPS Determines Risk of Childhood Wheeze and Asthma in 17q21 Risk Allele Carriers. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 205 (6). pp. 641-650. ISSN 1073-449X, 1535-4970
Full text not available from this repository. (Request a copy)Abstract
Rationale: In murine models, microbial exposures induce protection from experimental allergic asthma through innate immunity. Objectives: 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 T-helper cell type 2 (Th2), Th1, and Th17 cytokine expression at age 1 year was measured after stimulation of peripheral blood mononuclear cells with 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 first year of life was assessed by weekly diaries and asthma by questionnaire at age 6 years. Measurements and Main 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% confidence interval [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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EARLY-LIFE; ASSOCIATION; VARIANTS; EXPOSURE; CONTRIBUTE; CHILDREN; ALLERGY; DISEASE; innate immune response in children; 17q21 genotype; farm environment; unprocessed cow's milk; gut microbiome |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 28 Feb 2024 13:54 |
| Last Modified: | 28 Feb 2024 13:54 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58486 |
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