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Gene expression in placenta, peripheral and cord blood mononuclear cells from allergic and non-allergic women
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Inflammation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Immunology and Transfusion Medicine.
Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center of Paediatrics and Gynaecology and Obstetrics, Department of Gynaecology and Obstetrics in Linköping.
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2014 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The influence of maternal allergy on the development of immune responses and allergy in the offspring is not understood.

Objective: To investigate (i) if maternal allergy influences the gene expression locally in placenta, systemically in peripheral blood mononuclear cells (PBMC) and fetally in cord blood mononuclear cells (CBMC), (ii) if the gene expression in the placenta and PBMC influences the gene expression in CBMC and (iii) how the gene expression at birth relates to allergy development during  childhood.

Methods: A real-time PCR array was used to quantify forty immune regulatory genes in placenta, PBMC (gestational week 39) and in CBMC from 7 allergic and 12 non-allergic women and their offspring. Furthermore, quantitative real-time PCR was used to measure mRNA expression of Tbx21, GATA-3, Foxp3, RORC and CCL22 in CBMC, selected based on present PCR array results and previous protein findings in cord blood, in 13 children who developed and 11 children who did not develop allergy during childhood.

Results: The gene expression profile in the placenta revealed a T-helper (Th) 2-/anti-inflammatory environment as compared with gene expression systemically, in PBMC. Maternal allergy was associated with increased expression of p35 in PBMC and CBMC and p40 in placenta. Placental p35 expression correlated with fetal Tbx21 expression (Rho=-0.88, p<0.001) and maternal IL-5 expression in PBMC with fetal Galectin-1 (Rho=0.91, p<0.001) expression. Allergy development in the children was preceded by high mRNA expression of the Th2-associated chemokine CCL22 at birth.

Conclusion and clinical relevance: Gene expression locally and systemically during pregnancy influenced the offspring’s gene expression at birth, indicating an interplay between maternal and fetal immunity. Children developing allergy during childhood had an increased expression of the Th2-associated chemokine CCL22 at birth, indicating a Th2 skewing before disease onset. Maternal allergy was not associated with a Th2-dominance in placenta, PBMC or CBMC.

Place, publisher, year, edition, pages
2014.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-106219OAI: oai:DiVA.org:liu-106219DiVA: diva2:714660
Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2015-03-25Bibliographically approved
In thesis
1. Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring
Open this publication in new window or tab >>Immunological interactions between mother and child during pregnancy in relation to the development of allergic diseases in the offspring
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Pregnancy and allergic disease have both been postulated as T-helper 2 (Th2) phenomena. Thus, the increased propensity of allergic mothers to mount Th2-responses might generate favourable effects on the maintenance of pregnancy, but might also be unfavorable, as fetal exposure to a strong Th2 environment could influence the immune development in the offspring to a Th2-like phenotype, favouring IgE production and possibly allergy development later in life. The influence of the intrauterine environment on the immunity and allergy development in the offspring needs to be further investigated.

Aim: The aim of this thesis was to explore the Th1/Th2 balance in allergic and non-allergic women during pregnancy and its influence on the shaping of the Th1/Th2 profile in the neonate and the development of allergic diseases in the offspring.

Material and methods: The study group included 20 women with and 36 women without allergic symptoms followed during pregnancy (gestational week 10-12, 15-16, 25, 35, 39) and 2 and 12 months postpartum, and their children followed from birth to 6 years of age. The circulating Th1-like chemokines CXCL9, CXCL10, CXCL11, Th2-like chemokines CCL17, CCL18 and CCL22, and the allergen-induced secretion of interleukin-4 (IL-4), IL-5, IL-10, IL-13, Interferon-γ (IFN-γ), CXCL10 and CCL17 were measured by Luminex and ELISA. The allergen-specific and total IgE levels were quantified using ImmunoCAP Technology. mRNA expression of Th1-, Th2-, Treg- and Th17-associated genes were measured by PCR arrays and real-time PCR.

Results: We found that sensitised women with allergic symptoms had increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy as compared with postpartum. The non-sensitised women without allergic symptoms had elevated cat-induced IL-5 and IL-13 responses and lower birch- and cat-induced IFN-γ during pregnancy, but similar IgE levels as compared with postpartum.

Maternal total IgE levels during and after pregnancy correlated with cord blood (CB) IgE and CCL22 levels (regardless of maternal allergy status). Circulating CXCL11, CCL18 and CCL22 levels during pregnancy and postpartum correlated with the corresponding chemokine levels in the offspring at various time points during childhood. Maternal IL-5 expression in peripheral blood mononuclear cells (PBMC) was associated with neonatal Galectin-1, and placental p35 expression was negatively associated with neonatal Tbx21 expression. Increased mRNA expression of CCL22 in cord blood mononuclear cells (CBMC), and increased CCL17 and CCL22 levels in CB were observed in children later developing allergic symptoms and sensitisation as compared with children who did not. Development of allergic symptoms and sensitisation were associated with increased total IgE, CCL17, CCL18 and CCL22 levels during childhood.

Conclusions: Maternal allergy was associated with a pronounced Th2 deviation during pregnancy, shown as increased total IgE levels and birch- and cat-induced IL-5, IL-13 and CCL17 responses during pregnancy, possibly exposing their fetuses to a particular strong Th2 environment during gestation.

Correlations were shown between the maternal immunity during pregnancy and the offspring’s immunity at birth and later during childhood, indicating an interplay between the maternal and fetal immunity.

Allergy development during the first 6 years of life was associated with a marked Th2 deviation at birth and a delayed down-regulation of this Th2-skewed immunity during childhood.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2014. 98 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1405
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-106220 (URN)10.3384/diss.diva-106220 (DOI)978-91-7519-330-4 (ISBN)
Public defence
2014-05-22, Berzeliussalen, Campus US, Linköpings universitet, Linköping, 09:00 (Swedish)
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Available from: 2014-04-29 Created: 2014-04-29 Last updated: 2014-04-29Bibliographically approved

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Abelius, Martina SJanefjord, CamillaErnerudh, JanBerg, GöranMatthiesen, LeifDuchén, KarelNilsson, LennartJenmalm, Maria
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Division of Inflammation MedicineFaculty of Health SciencesDivision of Cell BiologyDepartment of Clinical Immunology and Transfusion MedicineDivision of Clinical SciencesDepartment of Gynaecology and Obstetrics in LinköpingAllergy Center
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