Background European cross-sectional studies have suggested that prenatal and postnatal farm exposure decreases the risk of allergic diseases in childhood. Underlying immunologic mechanisms are still ...not understood but might be modulated by immune-regulatory cells early in life, such as regulatory T (Treg) cells. Objective We sought to assess whether Treg cells from 4.5-year-old children from the Protection against Allergy: Study in Rural Environments birth cohort study are critical in the atopy and asthma-protective effect of farm exposure and which specific exposures might be relevant. Methods From 1133 children, 298 children were included in this study (149 farm and 149 reference children). Detailed questionnaires until 4 years of age assessed farming exposures over time. Treg cells were characterized as upper 20% CD4+ CD25+ forkhead box protein 3 (FOXP3)+ (intracellular) in PBMCs before and after stimulation (with phorbol 12-myristate 13-acetate/ionomycin or LPS), and FOXP3 demethylation was assessed. Atopic sensitization was defined by specific IgE measurements; asthma was defined by a doctor's diagnosis. Results Treg cells were significantly increased in farm-exposed children after phorbol 12-myristate 13-acetate/ionomycin and LPS stimulation. Exposure to farm milk was defined as a relevant independent farm-related exposure supported by higher FOXP3 demethylation. Treg cell (upper 20% CD4+ CD25+ , FOXP3+ T cells) numbers were significantly negatively associated with doctor-diagnosed asthma (LPS stimulated: adjusted odds ratio, 0.26; 95% CI, 0.08-0.88) and perennial IgE (unstimulated: adjusted odds ratio, 0.21; 95% CI, 0.08-0.59). Protection against asthma by farm milk exposure was partially mediated by Treg cells. Conclusions Farm milk exposure was associated with increased Treg cell numbers on stimulation in 4.5-year-old children and might induce a regulatory phenotype early in life, potentially contributing to a protective effect for the development of childhood allergic diseases.
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 Environmental factors may play important roles in asthma, but findings have been inconsistent. Objective The goal of this study was to determine the associations between early life ...exposures, environmental factors, and asthma in urban and rural children in southeast China. Methods A screening questionnaire survey was conducted in 7,164 children from urban Guangzhou and 6,087 from rural Conghua. In the second stage, subsamples of 854 children (419 from Guangzhou, 435 from Conghua) were recruited for a case-control study that included a detailed questionnaire enquiring on family history, early life environmental exposures, dietary habits, and laboratory tests (including histamine airway provocation testing, skin prick tests, and serum antibody analyses). House dust samples from 76 Guangzhou families and 80 Conghua families were obtained to analyze levels of endotoxins, house dust mites, and cockroach allergens. Results According to the screening survey, the prevalence of physician-diagnosed asthma was lower in children from Conghua (3.4%) than in those from Guangzhou (6.9%) ( P < .001). A lower percentage of asthma was reported in rural subjects compared with urban subjects (2.8% vs. 29.4%; P < .001) in the case-control study. Atopy (OR, 1.91 95% CI, 1.58-2.29), parental atopy (OR, 2.49 95% CI, 1.55-4.01), hospitalization before 3 years of age (OR, 2.54 95% CI, 1.37-4.70), high consumption of milk products (OR, 1.68 95% CI, 1.03-2.73), and dust Dermatophagoides farinae group 1 allergen (OR, 1.71 95% CI, 1.34-2.19) were positively associated with asthma. Living in a crop-farming family at < 1 year of age (OR, 0.15 95% CI, 0.08-0.32) and dust endotoxin levels (OR, 0.69 95% CI, 0.50-0.95) were negatively associated with asthma. Conclusions Rural children from an agricultural background exhibited a reduced risk of asthma. Early life exposure to crop farming and high environmental endotoxin levels might protect the children from asthma in southern China.
Background Environmental factors can affect the development of atopic dermatitis, and this was described to be already effective during pregnancy and in early life. An important early postnatal ...exposure is nutrition, although its association with allergic disease remains unclear. Objective We sought to determine prospectively whether early postnatal exposures, such as the introduction to complementary food in the first year of life, are associated with the development of atopic dermatitis, taking into account the reverse causality. Methods One thousand forty-one children who participated in the Protection Against Allergy–Study in Rural Environments birth cohort study were included in the current study. Atopic dermatitis was defined by a doctor's diagnosis reported by the parents of children up to 4 years of age, by questionnaires, and/or by positive SCORAD scores from 1 year of age and according to the age of onset within or after the first year of life. Feeding practices were reported by parents in monthly diaries between the 3rd and 12th months of life. Results The diversity of introduction of complementary food in the first year of life was associated with a reduction in the risk of having atopic dermatitis with onset after the first year of life (adjusted odds ratio for atopic dermatitis with each additional major food item introduced, 0.76; 95% CI, 0.65-0.88). The introduction of yogurt in the first year of life also reduced the risk for atopic dermatitis (adjusted odds ratio, 0.41; 95% CI, 0.23-0.73). Conclusion As early-life exposure, the introduction of yogurt and the diversity of food introduced in the first year of life might have a protective effect against atopic dermatitis.
Background Cross-sectional studies have suggested that prenatal farm exposures might protect against allergic disease and increase the expression of receptors of the innate immune system. However, ...epidemiologic evidence supporting the association with atopic dermatitis remains inconsistent. Objective To study the association between prenatal farm-related exposures and atopic dermatitis in a prospective study. We further analyzed the association between the expression of innate immune genes at birth and atopic dermatitis. Methods A total of 1063 children who participated in a birth cohort study, Protection against Allergy-Study in Rural Environments, were included in this study. Doctor diagnosis of atopic dermatitis was reported by the parents from 1 to 2 years of age by questionnaire. Gene expression of Toll-like receptors (TLRs) and CD14 was assessed in cord blood leukocytes by quantitative PCR. Results Maternal contact with farm animals and cats during pregnancy had a significantly protective effect on atopic dermatitis in the first 2 years of life. The risk of atopic dermatitis was reduced by more than half among children with mothers having contact with 3 or more farm animal species during pregnancy compared with children with mothers without contact (adjusted odds ratio, 0.43; 95% CI, 0.19-0.97). Elevated expression of TLR5 and TLR9 in cord blood was associated with decreased doctor diagnosis of atopic dermatitis. A significant interaction between polymorphism in TLR2 and prenatal cat exposure was observed in atopic dermatitis. Conclusion Maternal contact with farm animals and cats during pregnancy has a protective effect on the development of atopic dermatitis in early life, which is associated with a lower expression of innate immune receptors at birth.
Background There is evidence that gene expression of innate immunity receptors is upregulated by farming-related exposures. Objective We sought to determine environmental and nutritional exposures ...associated with the gene expression of innate immunity receptors during pregnancy and the first year of a child's life. Methods For the Protection Against Allergy: Study in Rural Environments (PASTURE) birth cohort study, 1133 pregnant women were recruited in rural areas of Austria, Finland, France, Germany, and Switzerland. mRNA expression of the Toll-like receptor (TLR) 1 through TLR9 and CD14 was assessed in blood samples at birth (n = 938) and year 1 (n = 752). Environmental exposures, as assessed by using questionnaires and a diary kept during year 1, and polymorphisms in innate receptor genes were related to gene expression of innate immunity receptors by using ANOVA and multivariate regression analysis. Results Gene expression of innate immunity receptors in cord blood was overall higher in neonates of farmers ( P for multifactorial multivariate ANOVA = .041), significantly so for TLR7 (adjusted geometric means ratio aGMR, 1.15; 95% CI, 1.02-1.30) and TLR8 (aGMR, 1.15; 95% CI, 1.04-1.26). Unboiled farm milk consumption during the first year of life showed the strongest association with mRNA expression at year 1, taking the diversity of other foods introduced during that period into account: TLR4 (aGMR, 1.22; 95% CI, 1.03-1.45), TLR5 (aGMR, 1.19; 95% CI, 1.01-1.41), and TLR6 (aGMR, 1.20; 95% CI, 1.04-1.38). A previously described modification of the association between farm milk consumption and CD14 gene expression by the single nucleotide polymorphism CD14/C-1721T was not found. Conclusion Farming-related exposures, such as raw farm milk consumption, that were previously reported to decrease the risk for allergic outcomes were associated with a change in gene expression of innate immunity receptors in early life.
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 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.
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.
Background The protective effect of Mycobacterium bovis BCG vaccination against infection and atopy varies between populations. Objective To identify differences in neonatal responses to BCG between ...diverse populations and study longitudinal associations with memory T-cell responses. Methods Cord blood mononuclear cells were collected from Papua New Guinean (PNG) and Western Australian (WA) newborns. Toll-like receptor (TLR)-2, TLR4, and TLR9 mRNA expression and in vitro BCG-stimulated (±IFN-γ priming) innate cytokine responses were compared. When PNG infants were 3 months old, PBMCs were stimulated in vitro with Mycobacterium -purified protein derivative (PPD) to determine memory T-cell responses. Results BCG-induced IL-10 and IFN-γ responses were significantly higher in cord blood mononuclear cells of PNG newborns, and TLR2 and TLR9 expression was significantly higher and TLR4 expression lower compared with WA newborns. High neonatal IL-10 and low IFN-γ responses to BCG were found to promote the development of PPD-memory TH 2 responses in infancy, whereas neonatal BCG-TNFα responses inhibited the development of PPD-IL 10 responses. When primed with IFN-γ, BCG-induced TNF-α, IL-12p70, and in particular IFN-γ responses were enhanced to a significantly higher extent in WA than in PNG newborns. In response to IFN-γ priming and BCG stimulation, natural killer cells of WA newborns produced IFN-γ, whereas natural killer cells of PNG newborns contributed only indirectly to this response. Conclusion Neonatal BCG-related innate immune responses control the differentiation of TH memory responses and vary between populations. This may explain differences in the effects of BCG vaccination between populations.
