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Prenatal farm exposure is related to the expression of receptors of the innate immunity and to atopic sensitization in school-age children - 17/08/11

Doi : 10.1016/j.jaci.2005.12.1307 
Markus Johannes Ege, MD a, , Christian Bieli, MD b, , Remo Frei, MSc c, Robert Theodoor van Strien, PhD a, Josef Riedler, MD d, Ellen Üblagger, MD e, Dieneke Schram-Bijkerk, MSc f, Bert Brunekreef, PhD f, Marianne van Hage, MD, PhD g, Annika Scheynius, MD, PhD h, Göran Pershagen, MD, PhD i, Marcus R. Benz, MD a, Roger Lauener, MD c, Erika von Mutius, MD a, Charlotte Braun-Fahrländer, MD b,  the PARSIFAL Study team
a From University Children’s Hospital Munich 
b Institute for Social and Preventive Medicine, University of Basel 
c Zurich University Children’s Hospital 
d Children’s Hospital, Schwarzach 
e Children’s Hospital, Salzburg 
f Institute for Risk Assessment Sciences, Utrecht University 
g Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and University Hospital, Stockholm 
h Clinical Allergy Research Unit, Department of Medicine, Karolinska Institutet and University Hospital, Stockholm 
i Institute of Environmental Medicine, Karolinska Institute, Stockholm 

Reprint requests: Markus Johannes Ege, MD, Dr von Haunersche Kinderklinik, Lindwurmstrasse 4, 80337 Munich, Germany.

Munich, Germany, Basel and Zurich, Switzerland, Schwarzach and Salzburg, Austria, Utrecht, the Netherlands, and Stockholm, Sweden

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.

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Key words : Asthma, allergy, atopic sensitization, gene expression, Toll-like receptors, CD14, farming, maternal exposure, microbial exposure

Abbreviations used : EPS, OR, PARSIFAL, TLR


Plan


 Supported by a research grant from the European Union (QLRT 1999-01391) and by funding from the Swedish Foundation for Health Care Science and Allergy Research, the Swiss National Foundation (grant no. 32-100324), and the Kühne-Foundation.
Disclosure of potential conflict of interest: D. Schram-Bijkerek has received grants from Parsifal EU projects. E. von Mutius has consultant arrangements with UCB and GlaxoSmithKline. All other authors—none disclosed.


© 2006  American Academy of Allergy, Asthma and Immunology. Publié par Elsevier Masson SAS. Tous droits réservés.
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Vol 117 - N° 4

P. 817-823 - avril 2006 Retour au numéro
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