Background Traditional farming represents a unique model situation to investigate the relationship of early-life farm-related exposure and allergy protection. Objectives To investigate associations ...between maternal farm exposures and cytokine production in cord blood (CB) mononuclear cells in a prospective multinational birth cohort of 299 farm and 326 nonfarm children and their families. Methods Supernatants from phorbol 12-myristate 13-acetate/ionomycin–stimulated CB mononuclear cells were assessed for the production of IFN-γ, TNF-α, IL-5, IL-10, and IL-12. Results Significantly higher levels of IFN-γ and TNF-α in farm compared with nonfarm children were found, whereas IL-5, IL-10, and IL-12 levels did not differ between study groups. Maternal contact with different farm animal species and barns and consumption of farm-produced butter during pregnancy enhanced the production of proinflammatory CB cytokines, whereas maternal consumption of farm-produced yogurt resulted in significant lower levels of IFN-γ and TNF-α in umbilical blood. Conclusion Maternal exposure to farming activities and farm dairy products during pregnancy modulated cytokine production patterns of offspring at birth.
Background Previous cross-sectional surveys have suggested that maternal exposure to animal sheds during pregnancy exerted a protective effect on atopic sensitization in children lasting until school ...age. Objective We sought to evaluate the effects of maternal exposure to animal sheds and other farm-related exposures during pregnancy on cord blood IgE levels in a prospective birth cohort. Methods Pregnant women living in rural areas in Austria, Finland, France, Germany, and Switzerland were recruited in the third trimester of pregnancy. Information on maternal farm-related exposures, nutrition, and health during pregnancy was obtained by means of interviews. Specific IgE levels for food and common inhalant allergens were assessed in cord blood of 922 children and peripheral blood samples of their mothers. Results Different sensitization patterns in cord blood of farm and nonfarm children were observed. In multivariable analysis consumption of boiled, but not unboiled, farm milk during pregnancy was positively associated with specific IgE to cow's milk independently from maternal IgE. In contrast, there was an inverse relationship between maternal exposure to animal sheds and cord blood IgE levels against seasonal allergens (adjusted odds ratio, 0.38; 95% CI, 0.21-0.70). This association was not confounded by maternal IgE levels. Maternal contact with hay enhanced the protective effect of exposure to animal sheds on IgE levels to grass pollen in cord blood. Conclusions Maternal exposure during pregnancy influences atopic sensitization patterns in cord blood. The (microbial) context of allergen contact possibly modifies the risk of atopic sensitization.
Atopic sensitization in the first year of life Depner, Martin, PhD; Ege, Markus J., MD; Genuneit, Jon, MD ...
Journal of allergy and clinical immunology,
03/2013, Letnik:
131, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background There is conflicting evidence on whether allergen-specific memory is primed prenatally, whether this priming affects persistent immunologic effects, and whether it is modulated by the ...first environmental exposures in infancy. Objective We sought to explore the course of atopic sensitization between birth and 12 months of age. Methods Specific IgE levels for 6 food and 13 common inhalant allergens were assessed in cord blood and 1-year blood samples in the Protection against Allergy–Study in Rural Environments (PASTURE) birth cohort including 793 children from rural regions of 5 European countries. Detailed information on children’s health, nutrition, and farm-related exposures was gathered by using a pregnancy questionnaire, 2 questionnaires at 2 and 12 months of age, and a diary covering the time in between. Results Sensitization was more common at 12 months of age than at birth for almost all specificities. On an individual level, persistent sensitization to the same allergens was rare (1%), whereas transient (only at birth, 11%) and incident (only at 12 months, 34%) sensitization was seen in substantial proportions of children. Associations of transient sensitization with maternal sensitization differed with the allergen specificities, with the strongest associations for food allergens (odds ratio OR, 10.6; 95% CI, 6.0-18.6) and the weakest associations for seasonal allergens (OR, 1.64; 95% CI, 0.94-2.86). Associations of maternal sensitization with incident sensitization were also seen. Incident sensitization was related to distinct prenatal and postnatal environmental exposures of mother and child, such as consumption of cereals for incident sensitization to seasonal allergens (OR, 0.66; 95% CI, 0.50-0.88). Conclusion IgE sensitization patterns change between birth and 12 months and are related to maternal and environmental influences.
Background Altered intakes of n-3 and n-6 polyunsaturated fatty acids were suggested to modulate allergic disease, but intervention trials yielded inconclusive results. Because allergies are primed ...in early infancy and in utero , the fetus might be more accessible to nutritional intervention strategies. Objective We sought to investigate how supplementation of pregnant women with a fish oil (FO) preparation modulates allergy-related immune parameters in mothers and offspring. Methods We performed a multicenter, randomized, double-blind, placebo-controlled trial. Three hundred eleven pregnant women received daily either FO with 0.5 g of docosahexaenoic acid and 0.15 g of eicosapentaenoic acid, 400 μg of methyl-tetra-hydrofolic acid, both, or placebo from the 22nd gestational week. TH 1/TH 2-related molecules were quantified in 197 maternal and 195 cord blood samples by using real-time RT-PCR. Data are given as geometric means 95% CIs. Results FO supplementation was associated with increased TGF-β mRNA in maternal (0.85 0.8-0.89; placebo: 0.68 0.64-0.72) and cord blood (0.85 0.81-0.9; placebo: 0.75 0.71-0.79). IL-1 (0.69 0.66-0.73; placebo: 0.83 0.79-0.88) and IFN-γ (0.54 0.51-0.57; placebo: 0.65 0.61-0.69) were decreased in mothers only ( P < .001). Cord blood mRNA levels of IL-4 (0.54 0.52-0.57; placebo: 0.64 0.61-0.68), IL-13 (0.61 0.58-0.65; placebo: 0.85 0.80-0.89), CCR4 (0.70 0.67-0.73; placebo: 0.88 0.84-0.92; all P < .001), and natural killer ( P < .001) and CCR3+ CD8+ T cells ( P < .04) were decreased in the FO group. Conclusion Supplementation with FO during pregnancy is associated with decreased mRNA levels of TH 2-related molecules in the fetus and decreased maternal inflammatory cytokines. We speculate that both effects are mediated by TGF-β.
Background It is currently discussed whether allergic sensitization may start in utero under the influence of the maternal immune system and environmental determinants. Objective To investigate the ...relationship between allergen-specific cord blood (CB) IgE levels, parental sensitization, CB cytokine production, and environmental influences. Methods As part of an ongoing multicenter birth cohort study, allergen-specific IgE antibodies against 20 common seasonal, perennial, and food allergens were measured in blood samples from 922 neonates, 922 mothers, and 835 fathers. Supernatants from stimulated CB cells were assessed for the production of IL-5, IFN-γ, IL-10, and TNF-α. Results Allergen-specific IgE antibodies were detectable in 23.9% of newborns. Contamination with maternal serum was excluded by several means of analyses, including the absence of IgA antibodies. Clear correlation between maternal and fetal IgE was found only for hen's egg, cow's milk, and soybean allergen. Fetal IgE correlated negatively with the level of IFN-γ production, but not with IL-5 and IL-10. Conclusion Allergen-specific IgE antibodies most probably of fetal origin are detectable in CB and correlate with a lowered CB IFN-γ production.
To the Editor: Epidemiologic studies suggest an association of occupational domestic cleaning with asthma.1,2 More recently, a correlation of nonprofessional use of cleaning sprays with adult asthma ...has also been reported for private households.3 In this study application of commonly used cleaning and air-refreshing sprays was found to be a major risk factor for asthma, but the relevance of these findings for children remains to be understood. Because of their small airway diameters, young children are particularly susceptible to respiratory symptoms. To this end, we performed an observational study in 4-year-old offspring from pregnant women participating in a multicenter, randomized, double-blind, placebo-controlled clinical trial described in detail elsewhere.4 Briefly, the effects of increased intakes of a fish oil preparation (0.5 g of docosahexaenoic acid and 0.15 g of eicosapentaenoic acid), 400 μg of 5-methyl-tetrahydrofolate, both, or placebo from the 22nd week of gestation until delivery and birth outcomes were assessed in the main trial. ...a selection bias with respect to allergic diseases and use of room disinfectants would not be expected.
Background Asthma is characterized by a TH 2 immune response. CD4+ CD25hi regulatory T cells (Tregs) have been proposed to prevent allergic diseases through suppression of TH 2 responses. Objective ...We sought to investigate the role of CD4+ CD25hi T cells in children with asthma. Methods CD4+ CD25hi Tregs and forkhead/winged-helix transcription factor FOXP3 mRNA levels were quantified in peripheral blood and bronchoalveolar lavage fluid (BALF) of 18 children with asthma, 10 children with chronic cough, and 13 control subjects without lung diseases. CD4+ CD25hi T cells were isolated from peripheral blood and BALF of asthmatic patients and control subjects, and their capacity to suppress proliferation and cytokine/chemokine production of autologous responder T cells was analyzed. Results CD4+ CD25hi T cells were decreased in BALF of asthmatic children compared with values in children with cough or control subjects. In children with asthma, inhaled corticosteroid treatment was associated with increased percentages of CD4+ CD25hi T cells in peripheral blood and BALF. Isolated BALF and peripheral blood CD4+ CD25hi T cells from nonasthmatic subjects suppressed proliferation and cytokine/chemokine production by CD4+ CD25− responder T cells. BALF CD4+ CD25hi T cells from asthmatic subjects failed to suppress proliferation and production of TH 2-associated cytokines and chemokines by CD4+ CD25− responder T cells, which was restored after use of inhaled corticosteroids. Conclusion These findings provide the first evidence that pulmonary CD4+ CD25hi Tregs are impaired in pediatric asthma. Clinical implications Pulmonary Tregs might represent a therapeutic target in pediatric asthma.
Understanding the links between genetic, epigenetic and non-genetic factors throughout the lifespan and across generations and their role in disease susceptibility and disease progression offer ...entirely new avenues and solutions to major problems in our society. To overcome the numerous challenges, we have come up with nine major conclusions to set the vision for future policies and research agendas at the European level.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK