Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children

Article (PDF Available)inJournal of Allergy and Clinical Immunology 117(4):817-23 · May 2006with61 Reads
DOI: 10.1016/j.jaci.2005.12.1307 · Source: PubMed
There is increasing evidence that environmental exposures determining childhood illnesses operate early in life. Prenatal exposure to a farming environment through the mother might also play an important role. We sought to investigate the role of maternal exposures to environments rich in microbial compounds for the development of atopic sensitization, asthma, and corresponding alterations in the innate immune system in offspring. In the children of the cross-sectional Prevention of Allergy Risk Factors for Sensitization in Children Related to Farming and Anthroposophic Life Style study, asthma and atopy were assessed by means of standardized questionnaires (n = 8263) and serum IgE measurements (n = 2086). In a subsample (n = 322) gene expression of Toll-like receptors (TLR2 and TLR4) and CD14 was assessed. Maternal exposures were defined through questionnaire information. Both atopic sensitization (adjusted odds ratio, 0.58; 95% CI, 0.39-0.86) and the gene expression of receptors of innate immunity were strongly determined by maternal exposure to stables during pregnancy, whereas current exposures had much weaker or no effects. A dose-response relation was found between the extent of upregulation of these genes and the number of different farm animal species the mother had encountered in her pregnancy. Each additional farm animal species increased the expression of TLR2, TLR4, and CD14 by a factor of 1.16 (95% CI, 1.07-1.26), 1.12 (95% CI, 1.04-1.2), and 1.10 (95% CI, 1.03-1.23), respectively. Maternal exposure to an environment rich in microbial compounds might protect against the development of atopic sensitization and lead to upregulation of receptors of the innate immune system. The underlying mechanisms potentially operating through the intrauterine milieu or epigenetic inheritance await further elucidation. When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.


FIG E1. Signal intensity of CD14 measurements and ‘no template controls.’DRn values, which indicate the
magnitude of signal generated by the PCR reaction, are given for number of PCR cycles for 12 and 5
representative experiments, respectively.
FIG E2. Prevalences of atopic sensitization, hay fever, and asthma for farm (black bars) and reference
(gray bars) children.
FIG E3. The x-axis shows deciles of EPS load per square meter of mattress (n 5 322). The y-axis shows
geometric means (dots) of gene expression of TLR2, TLR4, and CD14, respectively, which were normalized by
dividing by gene expression of 18s rRNA. In addition, the linear fit of the association (solid line), along with the
corresponding 95% CI (dashed line), is displayed. All analyses were adjusted for age, sex, family history of
atopy, parental education, environmental tobacco smoking, maternal smoking during pregnancy, number
of older siblings, contact with pets ever, child’s current exposure to a farming lifestyle, child’s exposure to
farm animals, and predominant farm milk consumption of the child.
    • "The tenants were interviewed about housing characteristics and repairs that had been made. Further information about housing and lifestyle characteristics was obtained from a sampling field form and the second-month-after-birth questionnaire (Ege et al., 2006 ). Weather and outdoor air data were provided by the Finnish Meteorological Institute and the Finnish Aerobiology Group. "
    [Show abstract] [Hide abstract] ABSTRACT: The objectives of this study were a) to assess the determinants that affect concentrations of the bacterial cell wall components 3-hydroxy fatty acids (3-OH FAs) and muramic acid and of total viable bacteria and actinomycetes in house dust; and b) to examine the seasonal variation and reproducibility of these bacterial cell wall components in house dust. A number of lifestyle and environmental factors, mostly not consistent for different bacterial measures but commonly including the type of dwelling and farming (number of livestock) explained up to 37% of the variation of the bacterial concentrations in 212 homes in Eastern Finland. The reproducibility of 3-OH FAs and muramic acid measurements in house dust were studied in five urban homes and were found to be generally high (ICC 74-84%). Temporal variation observed in repeated sampling of the same home throughout a year was more pronounced for 3-OH FAs determinations (ICC 22%) than for muramic acid (ICC 55-66%). We conclude that determinants vary largely for different types of bacterial measurements in house dust; the measured parameters represent different aspects of the bacterial content indoors. More than one sample is needed to describe bacterial concentrations in house dust in the home environment due to large temporal variation. This article is protected by copyright. All rights reserved.
    Full-text · Article · Jul 2014
    • "Maternal genetic variants may determine the prenatal environment and thus play a role in the development of health conditions in their offspring, particularly for diseases with onset early in life.14,15 Many prenatal factors have been associated with IgE levels later in life.16,17 It is, therefore, conceivable that maternal genetic variants may have an influence on IgE levels in school-age children, particularly for genes in the IL-4/IL-13 pathway, as there is evidence that cord blood IgE was a predictor for allergy and asthma later in life.18,19 "
    [Show abstract] [Hide abstract] ABSTRACT: Purpose We investigated maternal genetic effects of four IL-4/IL-13 pathway genes as well as their interactions with the "Western or Eastern lifestyles/environments" on IgE in Karelian children. Methods This study included 609 children and their mothers. Total IgE levels in children and mothers were measured and 10 single nucleotide polymorphisms (SNPs) in IL-4, IL-4Ra, IL-13, and STAT6 were genotyped in mothers and their children. Results The maternal G allele of IL-13 130 (rs20541) was significantly (P=0.001) associated with decreased IgE in children in the Karelian population (Pooling Finnish and Russian children), as well as in Finnish (P=0.030) and Russian children (P=0.018). The IgE levels were significantly (P=0.001) higher in Russian children whose mothers were homozygous for the G allele of the IL-4Ra 50 (rs1805010) SNP than that in Russian children of mothers who were AG heterozygotes or AA homozygotes. After accounting for children's genotypes, we observed interactive effects on children's IgE for maternal IL-13 130 genotypes (P=0.014) and maternal IL-4Ra 50 genotypes (P=0.0003) with "Western or Eastern" lifestyles/environments. With the adjustment for multiple comparisons using a false discovery rate (FDR) of 0.05, the interactive effect of the maternal IL-4Ra50 SNP was significant. Conclusion Maternal genetic variants in IL-4/IL-13 pathway genes, such as IL-13 130 and IL-4Ra50, influenced IgE levels in school children that were independent of the children's genetic effects. These effects differ in "Western or Eastern" environments.
    Full-text · Article · Jul 2014
    • "кже в работах, посвященных изменениям в иммунной системе плода под влиянием контакта матери с домашними животными [33, 34]. Исследователи, изучающие возникновение аллергологической патологии у детей от матерей, получавших антибиотикотерапию, полагают, что эта связь опосредована через изменение состава материнской микрофлоры [35]. M. J. Ege и соавт. [36] показали, что дети, чьи матери в период беременности имели контакт с сельскохозяйственными микроорганизмами, имеют более высокий уровень экспрессии Toll-подобных рецепторов (TLR2, TLR4 и CD14), отвечающих за распознавание грамположительных и грамотрицательных бактерий. Более того, авторами продемонстрировано, что эта связь имеет дозозав"
    Article · Apr 2014
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