Non-allergic Mothers Research Articles

T cell subsets in cord blood are influenced by maternal allergy and associated with atopic dermatitis

This study aimed to investigate the influence of maternal allergy on cord blood regulatory and effector T cells and to evaluate their role as a predictor of atopic dermatitis (AD) during the first 2yr of life. Seventy mother-infant pairs were recruited in this prospective birth cohort study (21 allergic and 49 non-allergic mothers). Cord blood samples were collected and assayed for the percentage of regulatory T cells (Treg), interferon-γ (IFN-γ), and interleukin-4 (IL-4) producing T cells (Th1 and Th2, respectively) using flow cytometry. Experiments were undertaken to assess the function of cord blood CD4(+) CD25(+) CD127(-) Treg cells by cell proliferation and cytokine responses. Their offspring at the age of 2yr old were evaluated by dermatologists to determine whether they had AD. During the first 2yr of life, 15.7% of the children developed a physician-diagnosed AD. A significantly increased percentage of Th2 cell was observed in cord blood of newborns with maternal allergy. Treg/Th2 ratio significantly decreased among the offspring of allergic mothers. Treg cell-associated suppression of Th2 response was attenuated in Der p1-stimulated CD4(+) CD25(-) T cells from the offspring of allergic mothers. Children with reduced Th1/Th2 (p=0.001, OR=0.37) and Treg/Th2 (p=0.001, OR=0.47) ratio in cord blood had a higher risk of developing AD. Maternal allergic status is associated with increased percentage of IL-4(+) CD4(+) T cells and a reduced Treg/Th2 ratio in cord blood at their children's birth, which may predispose to an increased risk for developing AD.

Neonatal protein kinase C zeta expression determines the neonatal T‐Cell cytokine phenotype and predicts the development and severity of infant allergic disease

Previous studies have demonstrated that reduced T-cell protein kinase C zeta (PKCζ) expression is associated with allergy development in infants born to atopic mothers. This study examined whether this relationship extends to a general population and addressed the basis for the association. A flow cytometry assay was developed for the measurement of T-cell PKCζ levels in PBMC, cord blood mononuclear cell and whole blood. Cord blood T-cell PKCζ levels were measured in 135 neonates, and allergic disease was evaluated by skin prick test and clinical examination at 12 months of age. Allergic children (particularly those with eczema) had significantly lower neonatal T-cell PKCζ expression than nonallergic children (P < 0.001). PKCζ levels predicted allergic disease with optimal specificity of 86% and sensitivity of 54%. The sensitivity was increased in the children of allergic mothers, who had significantly lower PKC levels than the children of nonallergic mothers. Cord blood PKCζ levels did not affect T-cell maturation in culture as assessed by CD45RA/RO expression, but low PKCζ expression was associated with reduced capacity for IFNγ production by matured T cells. Low cord blood PKC expression was further associated with increased IL-13 responses at 6 months. The findings suggest a potential role for the use of PKCζ levels in cord blood T cells as a presymptomatic test to predict allergy risk in children, particularly offspring of allergic mothers, and that the basis of this relationship is related to cytokine patterns in mature T cells.

The Pros and Cons of Airway Lining Fluid Composition Analysis

The Pros and Cons of Airway Lining Fluid Composition Analysis

Oral Tolerance Induced by Transfer of Food Antigens via Breast Milk of Allergic Mothers Prevents Offspring from Developing Allergic Symptoms in a Mouse Food Allergy Model

We examined whether maternal exposure to food antigens during lactation and maternal allergic status would affect the development of food allergy in offspring. OVA-sensitized or OVA-nonsensitized BALB/c female mice were exposed or unexposed to OVA during lactation. After weaning, their offspring were systemically sensitized twice with OVA and repeatedly given OVA by oral intubation. While 97.1% of the mice breastfed by OVA-nonsensitized and OVA-unexposed mothers developed allergic diarrhea, 59.7% of the mice breastfed by OVA-exposed nonallergic mothers during lactation and 24.6% of the mice breastfed by OVA-exposed allergic mothers during lactation developed food allergy. Furthermore, OVA was detected in breast-milk from OVA-exposed nonallergic mothers during lactation (4.6 ± 0.5 μg/mL). In addition, OVA-specific IgG1 titers were markedly increased in breast milk from allergic mothers (OVA-sensitized and OVA-unexposed mother: 11.0 ± 0.5, OVA-sensitized and OVA-exposed mother: 12.3 ± 0.3). Our results suggest that oral tolerance induced by breast milk-mediated transfer of dietary antigens along with their specific immunoglobulins to offspring leads to antigen-specific protection from food allergy.

Maternal cow’s milk consumption during pregnancy is inversely associated with the risk of cow’s milk allergy (CMA) in the offspring in a prospective birth cohort study

simultaneously. Even taking into account the age of introduction of cow's milk in the infant diet, high maternal milk consumption during pregnancy remained inversely associated with CMA in the offspring (OR = 0.59, 95% CI 0.38-0.92). When stratified according to maternal allergic rhinitis and asthma, only children of non-allergic mothers seemed to benefit from high maternal cow's milk consumption during pregnancy (OR 0.30, 95% CI 0.13-0.69). In children of allergic mothers, cow's milk consumption was neither risk nor a protective factor. Conclusion High maternal consumption of cow's milk products dur- ing pregnancy may protect children from developing CMA, more so than maternal consumption during lacta- tion. This association is evident only in children of non- allergic mothers. These results support data from animal studies on possible enhancement of tolerance already in utero.

Maternal allergic disease does not affect the phenotype of T and B cells or the immune response to allergens in neonates

It is hypothesized that the in utero environment in allergic mothers can affect the neonatal immune responses. The aim of this study was to analyse the effect of maternal allergic disease on cord blood mononuclear cell (CBMC) phenotype and proliferative responses upon allergen stimulation. Peripheral blood mononuclear cells (PBMC) from 12 allergic and 14 nonallergic mothers and CBMC from their children were analysed. In the mothers, we determined cell proliferation, production of IL-4 and expression of FOXP3 in response to allergen stimulation. In the children, we evaluated cell proliferation and FOXP3 expression following allergen stimulation. Furthermore, expression of different homing markers on T cells and regulatory T cells and maturity of the T cells and B cell subsets were evaluated directly ex vivo. The timothy- and birch-allergic mothers responded with increased proliferation and/or IL-4 production towards timothy and birch extract, respectively, when compared to nonallergic mothers. This could not be explained by impairment of FOXP3(+) regulatory T cells in the allergic mothers. CBMC proliferation and FOXP3 expression in response to allergens were not affected by the allergic status of the mother. Also, phenotype of T cells, FOXP3(+) regulatory T cells and B cells was not affected by the allergic status of the mother. Our results suggest that maternal allergic disease has no effect on the neonatal response to allergens or the phenotype of neonatal lymphocytes. The factors studied here could, however, still affect later development of allergy.

Modulation of in vivo and in vitro cytokine production over the course of pregnancy in allergic and non‐allergic mothers

Cytokines secreted during pregnancy may influence immune development of the foetus. This study aimed to determine if maternal allergy alters patterns of systemic cytokine production throughout and after pregnancy. Maternal plasma cytokines and allergen-specific production of interleukin (IL)-10, IL-13 and interferon (IFN)-gamma were measured in allergic (n = 63) and non-allergic (n = 70) pregnant women who had a full set of sequential peripheral blood samples collected at 20-, 30-, 36-wk gestation and 6-wk post-partum. Maternal allergy was strictly defined by both allergen sensitization and doctor-diagnosed asthma, eczema or rhinitis. IL-13 responses to allergen were higher for allergic mothers at all time-points (20 wk: p < 0.001; 30 wk: p = 0.001; 36 wk: p < 0.001; post-partum: p < 0.001). For the non-allergic group, IL-13 levels to house dust mite decreased from 20- to 36-wk gestation (Friedman ANOVA p = 0.012) and were significantly lower at 36 wk compared with post-partum (p = 0.002). In contrast, IL-13 production by allergic mothers did not change from 20 wk through to post-partum. For both allergic and non-allergic mothers, in vitro IFN-gamma production was lower at all pregnancy time-points compared with post-partum levels. Allergic women had an increased propensity for peripheral blood allergen-specific T helper-2 responses during pregnancy, and failed to downregulate these responses in comparison with non-allergic women. This may be a factor that contributes to the increased risk of atopy in infants born to allergic mothers.

TGF-beta(1), IL-10 and IL-4 in colostrum of allergic and nonallergic mothers.

To determine transforming growth factor (TGF) beta(1), interleukin (IL) 4, and IL-10 concentrations in human milk and to assess the relationship between allergic disorders in mothers and the content of the interleukins in their milk. Thirty allergic and 46 healthy mothers were included in the study. Colostrum was collected 2-3 days after delivery. Cytokine concentrations were determined with commercial enzyme-linked immunosorbent systems. TGF-beta(1)was found in milk from 23 women in the control group (53.49%) and 11 in the allergy group (37.93%). When TGF-beta(1) was present, the median concentration was higher in the allergy group than in the control (61.5 and 30.4 pg/mL, respectively; P < 0.004). IL-10 was present in the colostrum of all the women and the median IL-10 concentration did not differ between the allergy (50.5 pg/mL) and control (51.5 pg/mL) groups. The probability of occurrence of a positive IL-4 value in the allergy group was greater than in the control group (chi-squared [df=1] = 2.60, P < 0.053). Median IL-4 level did not differ significantly between the two groups (0.5 and 0.5 pg/mL respectively). TGF-beta(1) was detected less often in the colostrum of allergic mothers than in that of mothers without allergy (but the difference was not statistically significant). IL-4 was found more often in the colostrum of allergic mothers than nonallergic ones. The allergy status did not correlate with IL-10 concentration.

Breast feeding, parental allergy and asthma in children followed for 8 years. The PIAMA birth cohort study

Background:It is unclear how the association between breast feeding and asthma develops with age of the child and how this association over time is influenced by maternal or paternal allergy....

Cytokines in human colostrum and breast milk from allergic and non-allergic mothers and development of atopic diseases in infants

Cytokines in human colostrum and breast milk from allergic and non-allergic mothers and development of atopic diseases in infants

Pregnancy IFN‐γ responses to foetal alloantigens are altered by maternal allergy and gravidity status

During pregnancy, variations in maternal-foetal cellular interactions may influence immune programming. This study was carried out to determine if maternal responses to foetal alloantigens are altered by maternal allergic disease and/or previous pregnancies. For this cohort study, peripheral blood was collected from allergic (n = 69) and nonallergic (n = 63) pregnant women at 20, 30, 36-week gestation and 6-week postpartum (pp). Cord blood was collected at delivery. Mixed lymphocyte reactions were used to measure maternal cytokine responses [interleukin-6 (IL-6), IL-10, IL-13 and (interferon-gamma) IFN-gamma] at each time point towards foetal mononuclear cells. Maternal cytokine responses during pregnancy (20, 30 and 36 weeks) were suppressed compared to the responses at 6-week pp. The ratio of maternal IFN-gamma/IL-13 and IFN-gamma/IL-10 responses were lower during pregnancy. Allergic mothers had lower IFN-gamma responses at each time-point during pregnancy with the greatest difference in responses observed at 36-week gestation. When allergic and nonallergic women were further stratified by gravidity group, IFN-gamma responses of allergic multigravid mothers were significantly lower than nonallergic multigravid mothers during pregnancy. During normal pregnancy, peripheral T-cell cytokine responses to foetal alloantigens may be altered by both allergic status of the mother and previous pregnancies. These factors could influence the cytokine milieu experienced by the foetus and will be further explored in the development of allergic disease during early life.

Maternal allergy influences p38‐mitogen‐activated protein kinase activity upon microbial challenge in CD14+ monocytes from 2‐year‐old children

The development of allergic diseases is dependent on genetic and environmental factors. It has been shown previously that cord blood mononuclear cells (CBMCs) from infants with parental allergy have altered cytokine profiles upon bacterial encounter; it might be possible that such impairment persists during the early years of childhood. The aim of this study was to investigate anti-microbial responses with regard to p38-mitogen-activated protein kinase (MAPK) activity in CD14(+) monocytes and IL-6 release from mononuclear cells in the same group of children at birth and at 2 years of age. Methods Paired samples of CBMCs and peripheral blood mononuclear cells (PBMCs) were stimulated with either lipopolysaccharide (LPS) or peptidoglycan in vitro. CD14(+) monocytes were analysed for p38-MAPK activity by flow cytometry, and soluble IL-6 receptor, soluble glycoprotein130 and IL-6 release from PBMC cultures were quantified by ELISA. CBMCs from newborns with allergic mothers tended to have a lower IL-6 response following an LPS (P=0.09) challenge compared with the group without maternal allergy while p38-MAPK activation levels did not differ between the groups. PBMCs from 2-year-olds with allergic mothers released significantly less (P<0.05) IL-6 upon peptidoglycan stimuli compared with age-matched infants with non-allergic mothers. Infants with allergic mothers displayed markedly reduced CD14(+) monocyte p38-MAPK phosphorylation after LPS (P<0.05) and peptidoglycan (P<0.01) challenge. This altered anti-microbial response was attributed to maternal allergy rather than to being IgE-sensitized at 2 years of age. Monocytes from children with allergic mothers are less responsive to bacterial challenge than monocytes from children with non-allergic mothers, and this impairment persists during the first 2 years of infancy.

Effect of oral application of a probioticE. coli strain on the intestinal microflora of children of allergic mothers during the first year of life

Influence of intestinal colonization by a probiotic E. coli strain on the incidence of bacterial pathogens in stool and allergic symptoms during the 1st year of life was monitored in 3 groups: colonized children of allergic mothers (AC; n = 52), noncolonized children of allergic mothers (AN; n = 50), children of nonallergic mothers (NC; n = 42). Colinfant vaccine was administered within 2 d after birth, 3 x a week over a period of 4 weeks. Stool samples were examined after 2 d and at the age of 3, 6 and 12 months. At 3 months E. coli was present in 90 %, at 12 months in 73 % of AC. Pathogens were significantly less frequent on day 3 and at 3 months in AC vs. AN (15 vs. 61 %, p < 0.001; 15 vs. 38 %, p < 0.01) and vs. NC (15 vs. 63 %, p < 0.001; 15 vs. 53 %, p < 0.001). AC exhibited lower incidence of Staphylococcus epidermidis than AN on day 3 (6 vs. 31 %, p < 0.001) and of Klebsiella strains on day 3 and at 3 months (4 vs. 20 %, p < 0.05; 5 vs. 24 %, p < 0.01). AC showed a lower incidence of Pseudomonas aeruginosa than NC on day 3 (6 vs. 31 %, p < 0.01) and Klebsiella spp. on day 3 and at 3 months (4 vs. 22 %, p < 0.05; 5 vs. 45 %, p < 0.001). No significant differences were recorded after 6 and 12 months. The incidence of allergies was 3 % in AC, 26 % in AN (p < 0.01), and 10 % in NC.

Effect of cytokines in breast milk on infant during the first two-years of life

Purpose : Breast milk contains several components that provide specific immunity and affect the maturation of the infant's immune system. Allergic disease (AD), including atopic eczema, asthma, allergic rhinitis, and food allergy is characterized by an imbalance between cytokines produced by distinct T-helper cell subtypes. The aim of the study was to investigate the concentrations of cytokines and chemokines that were involved in allergic reactions in breast milk from allergic and nonallergic mothers and then analyse the effect of breastfeeding duration on the prevalence of allergic disease in the age of two. Methods : The breast milk samples were collected from mothers with AD (n=88) and without AD (n=47). Breast milk was collected at the second day (colostrum) and four weeks later (mature milk).The level of Interlukine (IL)-4, IL-5, IL-6, IL-8, IL-10, IL-13, TGF-β1, TGF-β2, RANTES in breast milk were determined by commercially available enzyme-linked immunosorbent assay (ELISA) kits according to the manufacturer's instructions. Results : Mothers with AD had a higher concentration of IL-8 in colostrum compared with those without AD (P=0.021). But, TGF-β1 and TGF-β2 were higher concentrated in colostrum of mother without AD (P=0.013, P=0.001). Whereas concentrations of other cytokines were not significantly different between the two groups. There was no association between levels of cytokines and chemokines in the breast milk and allergic development during the first 2 years of life in the infants. Conclusion : The higher concentration of TGF-β1 and TGF-β2 in colostrum from non-allergic mothers may explain the protective effect. But, the higher concentrations of IL-8 in colostrum from allergic mothers may in part explain the controversial results on the protective effect of breastfeeding against allergic diseases. We conclude that there is no convincing evidence form a relation between cytokines in breast milk and allergic diseases in infants. Longer follow-up are necessary to evaluate the effects of breast milk components on AD.

Effect Of Breast Milk Feeding From Allergic And Non-allergic Mothers On Infant During The First 4-years Of Life

Effect Of Breast Milk Feeding From Allergic And Non-allergic Mothers On Infant During The First 4-years Of Life

Transforming growth factor‐β1 and interleukin‐10 in breast milk and development of atopic diseases in infants

Precise relationship between breastfeeding and infant allergy is poorly understood. Objective Aim was to quantify TGF-beta(1) and IL-10 in colostrum and mature milk from allergic and non-allergic mothers and to verify relationship with allergic disease development. Mothers (13 allergics, nine controls) of 22 newborns participated to prospective study on development of children atopy. Colostrum and mature milk were assayed for TGF-beta(1) and IL-10 by ELISA. Children underwent paediatrician evaluation at 6 months of life. Data are presented as median values and range. A significant difference in concentration of TGF-beta(1) between colostrum (330, range 0-3400 pg/mL) and mature milk (215, range 0-2400 pg/mL) was observed in samples from allergic mothers (P=0.015). In mature milk TGF-beta(1) was significantly lower in allergic (215, range 0-2400 pg/mL) than in non-allergic mothers (1059, range 0-6250 pg/mL) (P=0.015). IL-10 was weakly expressed without significant differences between allergic (4.8, range 0-42 and 9.5, range 0-42 pg/mL in colostrum and in mature milk) and non-allergic mothers (0, range 0-42 pg/mL in colostrum and 0, range 0-42 pg/mL in mature milk). After 6 months 46% infants from allergic mothers, but none from controls, presented atopic dermatitis. TGF-beta(1) was significantly less secreted in mature milk of allergic mothers, while no difference in IL-10 was found. Particular cytokine patterns in milk could influence development of atopic diseases. Further immunological studies in this field are necessary.

Presence of IgE cells in human placenta is independent of malaria infection or chorioamnionitis.

We have shown previously that numerous IgE(+) macrophage-like cells are present in the villous stroma of full term placenta and that there was no difference in the amount of IgE(+) cells between allergic and non-allergic mothers. The presence of such an abundant number of IgE(+) cells in the placenta in allergic as well as non-allergic women suggests that the IgE is of some importance for a successful pregnancy outcome. Here we have investigated the IgE-pattern in 59 placentas from second and third trimesters from Sweden with different degrees of chorioamnionitis and 27 full term placentas from Ghana with and without malaria parasites. The immunohistochemical staining pattern for IgE looked similar to our previous study, with the IgE located on Hofbauer-like cells. We could not find any difference in the amount or distribution of IgE(+) cells between malaria-infected and non-infected placentas, nor between different degrees of chorioamnionitis. The IgE score in the placenta did not correlate with the levels of IgE in maternal serum or plasma. However, the IgE score was significantly higher in second- compared to third-trimester placentas (P = 0.03). This might reflect a maturation time-point in the fetus and in the intrauterine environment during the second trimester, or it might be associated with the increased number of intrauterine fetal deaths in the second trimester.

Consumption of fish, butter and margarine during pregnancy and development of allergic sensitizations in the offspring: role of maternal atopy

It has been suggested that changes in dietary habits, particularly increased consumption of omega-6 polyunsaturated fatty acids (PUFA) and decreased consumption of omega-3 PUFAs may explain the increase in atopic disease seen in recent years. Furthermore, it seems possible that it is mainly prenatal or very early life environmental factors that influence the development of allergic diseases. It has also been suggested that intrauterine risk factors may act differently if mother themselves suffer from allergic disease. The aim of this study was to investigate whether the consumption of fish, butter and margarine during pregnancy might influence the development of allergic sensitizations in the offspring. The study population was divided into the offspring of allergic and non-allergic mothers. This was a retrospective cohort study enrolling 295 offspring of allergic mothers and 693 of non-allergic mothers. Information regarding maternal intake of fish, butter and margarine during pregnancy as well as other prenatal and perinatal confounding factors were retrospectively assessed by parental report via a standardized questionnaire. Atopy was determined by skin-prick tests (SPT) to eight prevalent inhalant allergens and two foods. In the allergic mothers' group there is no clear correlation between maternal intakes of fish, butter and margarine and sensitizations to food or inhalants. In the non-allergic mothers' group there was no correlation between butter and margarine intake and food or inhalant sensitizations. On the contrary, a protective effect of fish intake on SPT positivity was observed. In particular, frequent maternal intake ('2-3 times/wk or more') of fish reduced the risk of food sensitizations by over a third (aOR 0.23; 95% CI: 0.08-0.69). A similar trend, even if not significant, was found for inhalants. Finally, even in the whole study population, i.e. allergic group plus non-allergic group, there was a similar trend between increased consumption of fish and decreased prevalence of SPT positivity for foods. This study shows that frequent intake of fish during pregnancy may contrast the development of SPT sensitizations for foods in the offspring of mothers without atopic disease. Therefore, larger prospective studies are needed, enrolling mothers with and without allergic disease, to confirm these results.

Breast milk fatty acids and allergic disease in preschool children: The Prevention and Incidence of Asthma and Mite Allergy birth cohort study

Better understanding of the association between early life lipid intakes and the development of allergic diseases is needed. We prospectively studied breast milk content of n-6, n-3, and trans fatty acids in relation to allergic symptoms at the ages of 1 and 4 years. Fatty acid content was determined in breast milk samples of 265 (158 allergic and 107 nonallergic) mothers of children participating in the Prevention and Incidence of Asthma and Mite Allergy study. Outcome variables studied were parental reported eczema at age 1 year, eczema at age 4 years, asthma at age 4 years, and, in a subgroup of 133 children, sensitization at age 4 years. In children of mothers with allergy, breast milk n-3 long chain polyunsaturated fatty acids and the ratio between n-3 and n-6 long chain polyunsaturated fatty acids were inversely associated with asthma and with persistent symptoms (eczema at age 1 year and eczema at age 4 years and/or asthma at age 4 years), but no associations between breast milk fatty acids and sensitization were observed. In children of mothers with allergy, also trans fatty acids tended to be inversely associated with allergic symptoms. In children of mothers without allergy, no associations between breast milk fatty acids and allergic symptoms were observed, but alpha-linolenic acid (18:3n-3) was positively associated with sensitization. In susceptible infants, the risk to develop allergic symptoms, but not the risk of sensitization, was modified by intake of n-3 long chain polyunsaturated fatty acids through breast milk.

Fetal growth promotion in allergic children

Several in vitro studies have suggested the presence of Th2-skewed immunity during pregnancy in infants with atopic diseases. Our study indicated that allergic infants showed a higher birth weight and shorter gestational period at birth than those of non-allergic peers. Moreover, allergic mothers gave birth to neonates whose birth weights and gestational ages were higher and shorter than those of the non-allergic mothers, respectively. Thus, our data clearly demonstrated the promotion of intrauterine growth, either in the allergic children, or allergic mothers. Such an intrauterine environment favorable for the fetal growth may also accelerate the development of allergic diseases in their offspring that are most probably caused by the Th2-oriented immunity.