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产前农场暴露与学龄儿童先天免疫受体的表达及特应性致敏有关。

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

作者信息

Ege Markus Johannes, Bieli Christian, Frei Remo, van Strien Robert Theodoor, Riedler Josef, Ublagger Ellen, Schram-Bijkerk Dieneke, Brunekreef Bert, van Hage Marianne, Scheynius Annika, Pershagen Göran, Benz Marcus R, Lauener Roger, von Mutius Erika, Braun-Fahrländer Charlotte

机构信息

University Children's Hospital Munich, Germany.

出版信息

J Allergy Clin Immunol. 2006 Apr;117(4):817-23. doi: 10.1016/j.jaci.2005.12.1307. Epub 2006 Feb 7.

Abstract

BACKGROUND

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.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

CLINICAL IMPLICATIONS

When assessing risk factors of allergies in an infant's medical history, attention must also be paid to environmental exposures affecting the mother.

摘要

背景

越来越多的证据表明,决定儿童疾病的环境暴露在生命早期就开始起作用。母亲在孕期接触农业环境也可能起到重要作用。

目的

我们试图研究母亲接触富含微生物化合物的环境对后代特应性致敏、哮喘的发生以及先天免疫系统相应改变的作用。

方法

在“儿童与农业及人智学生活方式相关的致敏危险因素预防”横断面研究的儿童中,通过标准化问卷(n = 8263)和血清IgE测量(n = 2086)评估哮喘和特应性。在一个子样本(n = 322)中评估Toll样受体(TLR2和TLR4)和CD14的基因表达。通过问卷信息确定母亲的暴露情况。

结果

母亲孕期接触畜舍强烈决定了特应性致敏(校正比值比,0.58;95%可信区间,0.39 - 0.86)和先天免疫受体的基因表达,而当前的暴露影响较弱或无影响。在这些基因上调程度与母亲孕期接触的不同农场动物种类数量之间发现了剂量反应关系。每增加一种农场动物种类,TLR2、TLR4和CD14的表达分别增加1.16倍(95%可信区间,1.07 - 1.26)、1.12倍(95%可信区间,1.04 - 1.2)和1.10倍(95%可信区间,1.03 - 1.23)。

结论

母亲接触富含微生物化合物的环境可能预防特应性致敏的发生并导致先天免疫系统受体上调。潜在通过子宫内环境或表观遗传遗传起作用的潜在机制有待进一步阐明。

临床意义

在评估婴儿病史中的过敏危险因素时,还必须关注影响母亲的环境暴露。

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