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Increased circulating paternal antigen-specific IFN-γ- and IL-4-secreting cells during pregnancy in allergic and non-allergic women
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.ORCID iD: 0000-0002-3993-9985
Linköping University, Department of Clinical and Experimental Medicine, Clinical Immunology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Obstetrics and gynecology. Östergötlands Läns Landsting, Centre of Paediatrics and Gynecology and Obstetrics, Department of Gynecology and Obstetrics in Linköping. Linköping University, Faculty of Health Sciences.
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2008 (English)In: Journal of Reproductive Immunology, ISSN 0165-0378, E-ISSN 1872-7603, Vol. 79, no 1, 70-78 p.Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: Allergic women have been reported to give birth to more children than non-allergic women, speculatively explained by the former's predisposition for Th2 polarization, possibly favoring pregnancy.

AIM: The aim of this study was to test the hypothesis that allergy is associated with more Th2-deviated responses to paternal antigens throughout pregnancy.

METHODS: Blood samples were collected on six occasions during pregnancy and two occasions postpartum (pp). Of the 86 women initially included, 54 women had a normal pregnancy and completed the sampling procedures. Eleven women fulfilled the strict criteria for allergy (allergic symptoms and circulating IgE antibodies to inhalant allergens) and 23 were strictly non-allergic (non-sensitized without symptoms). The numbers of blood mononuclear cells secreting IFN-gamma and IL-4, spontaneously and in response to paternal alloantigens, were compared between the groups.

RESULTS: The numbers of spontaneously as well as paternal antigen-induced IFN-gamma- and IL-4-secreting cells were similar in allergic and non-allergic pregnant women on all occasions. A similar increase in the numbers of both IFN-gamma- and IL-4-secreting cells were found in allergic and non-allergic women during pregnancy, both regarding spontaneous and paternal antigen-induced secretion.

CONCLUSIONS: This study does not support the hypothesis of a more pronounced Th2-deviation to paternal antigens in allergic pregnant women compared with non-allergic pregnant women, as measured by number of cytokine-secreting cells. The observed increase of both IFN-gamma- and IL-4-secreting cells during normal pregnancy may be interpreted as a Th2-situation, since the effects of IL-4 predominate over the effects of IFN-gamma.

Place, publisher, year, edition, pages
2008. Vol. 79, no 1, 70-78 p.
Keyword [en]
Pregnancy, Th2, Elispot, MLC
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-16134DOI: 10.1016/j.jri.2008.07.001ISI: 000260989000010PubMedID: 18752853OAI: oai:DiVA.org:liu-16134DiVA: diva2:133222
Available from: 2009-01-08 Created: 2009-01-07 Last updated: 2013-08-29
In thesis
1. Immune regulation during pregnancy in relation to allergy and in women undergoing in vitro fertilization
Open this publication in new window or tab >>Immune regulation during pregnancy in relation to allergy and in women undergoing in vitro fertilization
2012 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

During pregnancy, the fetus expresses both maternal and paternal antigens. To the mother, the paternal antigens are foreign, providing her immune system with an interesting challenge. The fact that the fetus is not normally attacked and rejected implies that mechanisms of tolerance must exist. Pregnancy has long been considered to cause a redirection of the maternal immune responses towards a less aggressive type. Allergic disease has also been associated with that same redirection of immune responses, suggesting that this deviation may be more pronounced in allergic women during pregnancy. Several observations support the concept of a role of the immune system in the etiology of unexplained infertility, associating a redirection of the immune responses towards a more aggressive type with pregnancy loss and pregnancy failure.

The aim of this thesis was to investigate the immune responses during pregnancy in allergic and non-allergic women, and in infertile women undergoing IVF treatment. We hypothesized that allergic women would have a more pronounced Th2-deviation than non-allergic women towards paternal antigens during pregnancy and that an unsuccessful outcome of IVF treatment would be associated with aberrations in circulating leukocyte populations and a paternal antigen-specific Th1 and Th17 bias.

An increased number of both spontaneous and paternal antigen-induced Th2-like cytokine-secreting cells in peripheral blood was associated with pregnancy in 54 women with pregnancies defined as normal. The allergic pregnant women did not have a more pronounced Th2-deviation than the non-allergic women, as measured by numbers of cytokine-secreting cells. However, when analyzing cytokine levels in cell supernatants, we did observe lower Th1 responses towards paternal antigens in the allergic compared with non-allergic women. Additionally, allergy was associated with a reduced capacity to induce anti-inflammatory IL-10 responses towards paternal antigens.

In 25 infertile women undergoing IVF, the peak levels of the majority of paternal antigen-induced cytokines and leukocyte populations investigated coincided with the maximal levels of gonadotropins administered during IVF treatment, suggesting that controlled ovarian hyper-stimulation has a general stimulatory effect on the immune system and that it may be regarded as an inflammatory state. During the treatment, no differences were found regarding cytokine responses to paternal antigens in peripheral blood or the numbers or proportions of circulating leukocyte populations between women with a successful or unsuccessful outcome of IVF. We did see higher numbers of Th2-associated cytokine secreting cells and a lower proportion of lymphocytes in the pregnant compared with the non-pregnant women four weeks after embryo transfer, however, in line with previous findings of immune modulation during pregnancy.

In conclusion, normal pregnancy seems to be characterized by a less aggressive type of immune responses, possibly more pronounced in allergic women. This may be of importance for the in utero influences on childhood allergy development. An unsuccessful outcome of IVF does not appear to be associated with a more aggressive type of immune responses towards paternal antigens or aberrations in circulating leukocyte populations, although this should be confirmed in a larger study. The results in this thesis also indicate that the hormonal therapy during IVF treatment has a stimulatory effect on the immune system, generating an inflammatory state.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2012. 71 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1346
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-85642 (URN)978-91-7519-736-4 (ISBN)
Public defence
2012-12-05, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 13:00 (Swedish)
Opponent
Supervisors
Available from: 2012-11-26 Created: 2012-11-26 Last updated: 2013-08-29Bibliographically approved

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Persson, MarieEkerfelt, ChristinaErnerudh, JanMatthiesen, LeifJenmalm, MariaJonsson, YvonneSandberg, MartinaBerg, Göran

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Clinical ImmunologyFaculty of Health SciencesObstetrics and gynecologyDepartment of Gynecology and Obstetrics in LinköpingPediatrics
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