[Truncated abstract] The dramatic increase in the expression of allergic diseases such as asthma and allergy over the last 20-30 years has highlighted the urgent need to identify causative factors. It was hypothesised that direct immune interactions between mother and fetus contribute to the cytokine milieu of pregnancy, thus influencing immune maturation after birth. Further it was speculated that the cytokine responses produced as a result of maternalfetal interactions are Th-2 skewed in women allergic disease, which programmes their offspring towards developing an allergic phenotype after birth. To test this hypothesis a cohort of 169 pregnant women were recruited at 20 weeks gestation and defined as allergic or non-allergic based on both clinical history and skin prick test sensitisation. These women and their infants were followed up throughout pregnancy (20 weeks, 30 weeks, 36 weeks gestation and 6 weeks post-partum) and up to 2.5 years of age. Mixed lymphocyte reactions (MLR) were used to measure maternal cytokine (IL-6, IL-10, IL-13 and IFN-) and lymphoproliferative responses to fetal alloantigens at each pregnancy time-point. Human leukocyte antigen (HLA) typing of mothers and infants were performed to assess the effect of HLA mismatch on maternal MLR responses to their fetus. After delivery, mononuclear cells (MNC) were isolated from cord blood (CB) and stimulated with allergens, mitogen and toll-like receptor (TLR) ligands. .... As IL-6 also participates in adaptive immunity by promoting Th-2 differentiation it is proposed that the production of IL-6 as a results of maternal encounters with paternal antigens during pregnancy, contribute to the Th-2 skewed responses observed universally in most infants at birth. Associations between maternal-fetal interaction and clinical outcomes in infancy: Although clinical signs of allergy in infancy were not the main outcome measure of this thesis, there were interesting, yet complex relationships between the production of these maternal cytokines towards the fetus and allergic disease at infant follow-ups. Increased maternal IFN-¿ to fetal alloantigen was associated with asthma at 2.5 years and a trend towards recurrent wheeze at 12 months. In contrast decreased maternal IL-13 production was associated with IgE mediated food allergy at 12 months. Adjusting for maternal allergy and other potential confounders including infant gender, method of delivery, HLA mismatch, and paternal allergy did not account for these relationships. Further follow-ups of these infants are required to determine if these relationship last in to early childhood. In conclusion, the findings of this thesis provides further support for the hypothesis that immune responses at birth are programmed prenatally, and that this programming has implications later in life. Importantly, the placenta is the immunologically active interface between mother and fetus during pregnancy. Therefore it is emphasised that there is a crucial need for future research to focus on early immune programming at the placental level before the aetiological pathways of immune mediated diseases can be fully elucidated.
| Identifer | oai:union.ndltd.org:ADTP/281361 |
| Date | January 2009 |
| Creators | Breckler, Liza Anne |
| Publisher | University of Western Australia. School of Paediatrics and Child Health |
| Source Sets | Australiasian Digital Theses Program |
| Language | English |
| Detected Language | English |
| Rights | Copyright Liza Anne Breckler, http://www.itpo.uwa.edu.au/UWA-Computer-And-Software-Use-Regulations.html |
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