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Early-life EBV infection protects against persistent IgE sensitization.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Stockholm University, Faculty of Science, The Wenner-Gren Institute , Immunology.
Department of Epidemiology, Swedish Institute for Infectious Disease Control, Solna, Sweden.
Department of Clinical Science and Education, Sodersjukhuset, Karolinska Institutet and Sachs' Children's Hospital, Stockholm, Sweden.
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2010 (English)In: The Journal of allergy and clinical immunology, ISSN 1097-6825, Vol. 125, no 2, 433-8 p.Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Infection with EBV has previously been implicated in influencing allergic disorders, but its precise role remains contradictory. The timing of primary infection may contribute to the discrepancies. OBJECTIVE: This study aimed at investigating whether the time-point of primary EBV infection during childhood could be of importance in modulating the risk of developing IgE sensitization. METHODS: A total of 219 Swedish infants were followed prospectively to 5 years of age with clinical examinations, skin prick testing, specific IgE analyses, and determination of serostatus against EBV. RESULTS: After analysis of the children's EBV serostatus, we found that 5-year-olds who were infected with EBV before the age of 2 years were at a significantly lower risk of being persistently IgE-sensitized-that is, sensitized at both 2 and 5 years of age (adjusted odds ratio, 0.34; 95% CI, 0.12-0.94). In contrast, contraction of EBV after 2 years of age was highly associated with late-onset IgE sensitization (adjusted odds ratio, 4.64; 95% CI, 1.57-13.69). Persistently sensitized 5-year-olds had higher specific-IgE levels than children with late-onset IgE sensitization (P < .01). CONCLUSION: Our data support the value of early-life microbial exposure for protection against the development of IgE sensitization and underscore the proximate postnatal years as an important period during which EBV could contribute to an allergo-protective immune profile.

Place, publisher, year, edition, pages
2010. Vol. 125, no 2, 433-8 p.
National Category
Natural Sciences
Identifiers
URN: urn:nbn:se:su:diva-33003DOI: 10.1016/j.jaci.2009.09.033PubMedID: 19963258OAI: oai:DiVA.org:su-33003DiVA: diva2:282153
Available from: 2009-12-18 Created: 2009-12-18 Last updated: 2012-05-02Bibliographically approved
In thesis
1. Microbial and maternal influences on allergic sensitization during childhood: defining a role for monocytes
Open this publication in new window or tab >>Microbial and maternal influences on allergic sensitization during childhood: defining a role for monocytes
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Allergic diseases are influenced by genetics and the environment. Maternal allergy appears to confer a higher risk for allergic sensitization than paternal allergy, suggesting an in utero influence. A decrease in particular infections or a lower exposure to microbial components during infancy is suggested to contribute to the high allergy prevalence in affluent societies. Toll-like receptors (TLR) 2 and 4 recognize peptidoglycan (PGN) and LPS respectively, are expressed on e.g. monocytes, and have been implicated in modulating the risk of IgE-sensitization. This thesis aimed to study the influence of maternal allergy and early microbial exposure on monocyte function and allergic sensitization during childhood.

Blood samples from children participating in a prospective allergy cohort were used. Two-year old infants with allergic mothers had lower IL-6 production and reduced activation of the TLR-signalling intermediate p38-MAPK in response to PGN than children with non-allergic mothers. In 5-year old children, allergic disease and not maternal allergy influenced monocytic TLR2-regulation. Five-year olds who were seropositive for Epstein-Barr virus (EBV) at 2-years of age had a lower risk of persistent IgE-sensitization while EBV contraction after 2-years of age related to a higher risk of IgE-sensitization. Upon in vitro stimulation, NK cells from EBV+ 2-year olds produced lower IFN-g levels. EBV+ 2-year olds had also lower systemic IFN-g. In comparison to CD14++CD16- monocytes, CD14+CD16+ cells induced NK-cell IFN-g more potently in vitro, and EBV+ infants tended to have lower proportions of these CD14+CD16+ monocytes.

This thesis highlights the importance of early-life microbial (EBV) exposure for a proper allergy-protective immunity. Also, maternal allergic heredity appears to influence monocytic microbial responses in early infancy. All these aspects relate to altered monocyte functionality, which suggest that they could have a role in allergic sensitization.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University, 2009. 81 p.
Keyword
Monocytes, allergic sensitization, maternal allergy, Toll-like receptor, p38-MAPK, IL-6, Epstein-Barr virus, early-life microbial exposure, NK cells, IFN-γ
National Category
Immunology in the medical area
Research subject
Immunology
Identifiers
urn:nbn:se:su:diva-27620 (URN)978-91-7155-872-5 (ISBN)
Public defence
2009-06-12, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 8 C, Stockholm, 13:00 (English)
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Available from: 2009-05-21 Created: 2009-05-11 Last updated: 2012-03-13Bibliographically approved

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