| 1. |
- Abrahamsson, Thomas, 1968-
(author)
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Can Lactobacillus Reuteri Prevent Allergic Disease in Early Childhood?
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Background: An altered microbial exposure may be partly responsible for the increase of allergic diseases in populations with a western lifestyle. Activation of the immune system by microbes early in life is probably required for an accurate maturation of the immune system. Probiotics, live bacteria which are considered to confer health when ingested, have been suggested to prevent eczema and sensitisation infants.Aim: The general aim of this thesis was to assess the effect of oral supplementation with the probiotic bacterium Lactobacillus reuteri (L. reuteri) in infancy on the development of allergic disease and sensitisation during the first 2 years of life and to examine mechanisms possibly underlying eventual effects on allergic manifestations.Subjects: The thesis is based on results obtained from a prospective double-blind placebo-controlled multicenter trial, comprising 232 families with allergic disease, of whom 188 completed the study.Methods: The families were recruited at the antenatal clinic, and the mothers received L. reuteri ATCC 55730 (1 x 108 colony forming units) or placebo daily from gestational week 36 until delivery. Their babies then continued with the same study product from birth until 12 months of age and were followed up for another year. The primary outcomes were allergic disease, with or without positive skin prick test or circulating IgE to food allergens. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, employing conventional cultivation methods. Cytokines and IgA antibodies were analysed in colostrum and mature milk from the mothers with ELISA, and Na/K- ratio in breast milk with ion selective electrodes. Circulating Th1/Th2-associated chemokines were analysed in cord and peripheral blood in the infants with Luminex or ELISA technique.Results: The incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L. reuteri group had a lower cumulative incidence of IgE-associated allergic disease, 20% versus 35% (p=0.04), and less IgE-associated eczema during the second year, 8% versus 20% (p=0.02). The prevalence of L. reuteri was higher during the first year of life in stool samples from infants, as well as in colostrum, in the active as compared to the placebo treated group. Colostrum from L. reuteri supplemented mothers had lower levels of TGF-β2, and low levels of this cytokine were associated with less sensitisation. Low Th1- and high Th2-associated chemokine levels preceded allergic disease. The presence of L. reuteri in stool was associated with lower levels of the Th2-associated chemokines CCL17 and CCL22 and higher levels of the Th1-associated CXCL11.Conclusion: Although a preventive effect of probiotics on infant eczema was not confirmed, the L. reuteri treated infants had lower incidence of IgE-associated allergic disease at two years of age, and therefore possibly run a reduced risk to develop later respiratory allergic disease. The mechanisms underlying this effect require further elucidation.
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| 2. |
- Abrahamsson, Thomas, et al.
(author)
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Low diversity of the gut microbiota in infants with atopic eczema
- 2012
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In: Journal of Allergy and Clinical Immunology. - New York, USA : Elsevier BV. - 0091-6749 .- 1097-6825. ; 129:2, s. 434-U244
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is debated whether a low total diversity of the gut microbiota in early childhood is more important than an altered prevalence of particular bacterial species for the increasing incidence of allergic disease. The advent of powerful, cultivation-free molecular methods makes it possible to characterize the total microbiome down to the genus level in large cohorts. OBJECTIVE: We sought to assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to atopic eczema development. METHODS: Microbial diversity and composition were analyzed with barcoded 16S rDNA 454-pyrosequencing in stool samples at 1 week, 1 month, and 12 months of age in 20 infants with IgE-associated eczema and 20 infants without any allergic manifestation until 2 years of age (ClinicalTrials.gov ID NCT01285830). RESULTS: Infants with IgE-associated eczema had a lower diversity of the total microbiota at 1 month (P= .004) and a lower diversity of the bacterial phylum Bacteroidetes and the genus Bacteroides at 1 month (P= .02 and P= .01) and the phylum Proteobacteria at 12 months of age (P= .02). The microbiota was less uniform at 1 month than at 12 months of age, with a high interindividual variability. At 12 months, when the microbiota had stabilized, Proteobacteria, comprising gram-negative organisms, were more abundant in infants without allergic manifestation (Empirical Analysis of Digital Gene Expression in R edgeR test: P= .008, q= 0.02). CONCLUSION: Low intestinal microbial diversity during the first month of life was associated with subsequent atopic eczema.
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| 3. |
- Abrahamsson, Thomas, et al.
(author)
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Low gut microbiota diversity in early infancy precedes asthma at school age
- 2014
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 44:6, s. 842-850
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Journal article (peer-reviewed)abstract
- Background Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. Objective To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. Methods The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1week, 1month and 12months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7years of age (ClinicalTrials.gov ID NCT01285830). Results Children developing asthma (n=8) had a lower diversity of the total microbiota than non-asthmatic children at 1week (P=0.04) and 1month (P=0.003) of age, whereas allergic rhinoconjunctivitis (n=13), eczema (n=12) and positive skin prick reactivity (n=14) at 7years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Conclusion and Clinical Relevance Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood.
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| 4. |
- Abrahamsson, Thomas, et al.
(author)
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No effect of probiotics on respiratory allergies : a seven-year follow-up of a randomized controlled trial in infancy
- 2013
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 24:6, s. 556-561
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Journal article (peer-reviewed)abstract
- Background: Supplementation with the probioticLactobacillus reuteri reduced the incidence of IgE-associated allergic disease in infancy. This treatment might therefore also reduce the risk of asthma and allergic rhinoconjunctivitis in school age.Objective: To evaluate whether perinatal and infant supplementation withL.reuteri reduced the prevalence of respiratory allergic disease in school age and to explore whether this supplementation was associated with any long-term side effects.Methods: A randomized, placebo-controlled trial with oral supplementation withL.reuteriATCC 55730 (1x10(8)CFU) during the last month of gestation and through the first year of life comprising 232 families with allergic disease, of whom 184 completed a 7-yr follow-up. The primary outcomes at 7yr of age were allergic disease and skin prick test reactivity (ClinicalTrials.govID NCT01285830).Results: The prevalence of asthma (15% in the probiotic vs. 16% in placebo group), allergic rhinoconjunctivitis (27% vs. 20%), eczema (21% vs. 19%) and skin prick test reactivity (29% vs. 26%) was similar in the probiotic and placebo group. Growth indices and gastrointestinal symptoms were similar in the two groups. No severe adverse events were reported.Conclusion: The effect ofL.reuteri on sensitization andIgE-associated eczema in infancy did not lead to a lower prevalence of respiratory allergic disease in school age. Thus, the effect ofL.reuteri on the immune system seems to be transient. Administration ofL.reuteri during the last weeks of gestation and in infancy was not associated with any long-term side effects.
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| 5. |
- Abrahamsson, Thomas R, et al.
(author)
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Probiotic lactobacilli in breast milk and infant stool in relation to oral intake during the first year of life
- 2009
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In: Journal of pediatric gastroenterology and nutrition. - : Lippincott Williams & Wilkins. - 1536-4801 .- 0277-2116. ; 49:3, s. 349-354
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Journal article (peer-reviewed)abstract
- OBJECTIVES: This is to identify factors affecting the prevalence of Lactobacillus reuteri in maternal faeces and breast milk and infant faeces after oral supplementation with L reuteri and to assess the influence on microbial ecology, particularly Clostridium difficile and Bifidobacterium colonization. MATERIALS AND METHODS: In this double-blind trial, 232 mothers with a family history of atopic disease were randomized to a daily intake of either L reuteri American-type culture collection (ATCC) 55730 (1 x 10 colony-forming units [CFU]) or placebo for the last 4 weeks of pregnancy. Their babies then continued with the same study product daily from birth until 12 months of age. Bacterial counts and prevalence were assessed in maternal breast milk and faeces and infant faeces, using conventional cultivation methods. RESULTS: The prevalence of L reuteri was higher during the first year of life in the stool samples from infants in the active as compared with the placebo-treated group. The highest prevalence was recorded at 5 to 6 days of age (82% in the treated vs 20% in the placebo group, P < 0.001). Lactobacillus reuteri was isolated from 12% and 2%, respectively, in the colostrum samples (P < 0.05). Breast-feeding seemed to reduce faecal L reuteri counts, although antibiotics did not influence the levels of L reuteri. The administration of L reuteri did not affect bifidobacteria or C difficile colonization. CONCLUSION: Lactobacillus reuteri may be detected in breast milk after oral supplementation to the mother and in almost all infants after oral supplementation during the first year of life, as well as occasionally in many untreated infants.
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| 6. |
- Abrahamsson, Thomas R, 1968-, et al.
(author)
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Probiotics in prevention of IgE-associated eczema : a double-blind, randomized, placebo-controlled trial
- 2007
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 119:5, s. 1174-1180
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Journal article (peer-reviewed)abstract
- BACKGROUND: An altered microbial exposure may underlie the increase of allergic diseases in affluent societies. Probiotics may alleviate and even prevent eczema in infants. OBJECTIVE: To prevent eczema and sensitization in infants with a family history of allergic disease by oral supplementation with the probiotic Lactobacillus reuteri. METHODS: Double-blind, randomized, placebo-controlled trial, which comprised 232 families with allergic disease, of whom 188 completed the study. The mothers received L reuteri ATCC 55730 (1 x 10(8) colony forming units) daily from gestational week 36 until delivery. Their babies then continued with the same product from birth until 12 months of age and were followed up for another year. Primary outcome was allergic disease, with or without positive skin prick test or circulating IgE to food allergens. RESULTS: The cumulative incidence of eczema was similar, 36% in the treated versus 34% in the placebo group. The L reuteri group had less IgE-associated eczema during the second year, 8% versus 20% (P = .02), however. Skin prick test reactivity was also less common in the treated than in the placebo group, significantly so for infants with mothers with allergies, 14% versus 31% (P = .02). Wheeze and other potentially allergic diseases were not affected. CONCLUSION: Although a preventive effect of probiotics on infant eczema was not confirmed, the treated infants had less IgE-associated eczema at 2 years of age and therefore possibly run a reduced risk to develop later respiratory allergic disease. CLINICAL IMPLICATION: Probiotics may reduce the incidence of IgE-associated eczema in infancy.
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| 7. |
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| 8. |
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| 9. |
- Aniansson Zdolsek, Helena, 1961-, et al.
(author)
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Expression of the T–cell markers CD3, CD4 and CD8 in healthy and atopic Children during the first 18 months of life
- 1999
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 119:1, s. 6-12
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Journal article (peer-reviewed)abstract
- Background: There is little information available about the development of T–cell immunity in healthy and atopic children. We have studied prospectively the mean fluorescence intensity of the T–cell receptor complex–associated CD3, CD4 and CD8 in relation to atopic family history (AFH) and the development of atopic disease.Methods: Children with a defined AFH (n = 172) were followed from birth to 18 months and the cumulative history of atopic disease was recorded. Blood samples were obtained at birth and at 18 months, and in a subgroup of 78 children also at 3, 6 and 12 months. Multicolour flow cytometry was used to analyse pan T–cells (CD3+CD45+CD14–), T–helper–(CD3+CD4+) and T–cytotoxic–(CD3+CD8+) cells.Results: At 18 months, 31 children were atopic and 118 non–atopic. Children who developed atopic disease had a higher CD4 expression (mean fluorescence intensity, MFI) on CD4+CD3+ lymphocytes at birth and at 3 months, particularly as compared with non–atopic children without AFH. Furthermore, the CD3 expression on CD3+CD45+CD14– lymphocytes increased more slowly with age in children with double atopic heredity, as compared with children with no or only one atopic family member.Conclusions: The higher expression of the CD4 receptor in early infancy in children who developed atopic disease compared with non–atopics suggests a delayed expression in T–helper cells. Children with a strong AFH had a slower increase in the expression of CD3, indicating a delayed T–cell maturation.
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| 10. |
- Annus, T, et al.
(author)
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Wheezing in relation to atopy and environmental factors in Estonian and Swedish schoolchildren
- 2001
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 31:12, s. 1846-1853
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Journal article (peer-reviewed)abstract
- Background: The prevalence of asthma and allergic diseases is significantly lower in post socialist Eastern Europe than in Western industrialized countries. The reason for this difference is largely unknown. Different types of childhood wheezing could be related to different risk factors. Objective: To compare the prevalence of respiratory symptoms, asthma and atopic diseases among Estonian and Swedish schoolchildren and to evaluate characteristics for wheezing in the two countries. Methods: In a prevalence study, population-based random samples of 10-11-year-old schoolchildren in Tallinn (n = 979), Estonia and in Link÷ping (n = 911) and ╓stersund (n = 1197), Sweden were studied by a parental questionnaire and skin prick tests (SPT). All 275 children with wheeze in the past 12 months and 710 randomly selected controls within the original cohorts were invited to a case-control study involving a parental questionnaire, examination for flexural dermatitis and bronchial challenge with hypertonic saline. The study adhered to the International Study of Asthma and Allergies in Childhood (ISAAC) Phase II protocol. Results: The prevalence of current wheezing was similar (8-10%) in the three centres, while diagnosed asthma and atopic symptoms were more common in Sweden and cold-related respiratory symptoms were more prevalent in Estonia. Frequent wheezing was more common in Sweden than in Estonia (but significantly so only in ╓stersund). Wheezing children in Sweden had a high rate of positive SPT (49% in Link÷ping and 58% in ╓stersund) bronchial hyper-responsiveness (BHR) (48% in Link÷ping and ╓stersund) and anti-asthmatic treatment (63% in Link÷ping and 81% in ╓stersund). In Estonia, the proportion of wheezing children with positive SPT, BHR and anti-asthmatic treatment was only 26%, 13% and 17%, respectively. Domestic crowding was inversely related to wheezing in one of the study areas (╓stersund). The mean baseline forced expiratory volume in one second (FEV1) was higher in Estonia than in Sweden, both in wheezing and non-wheezing children. Conclusions: Our study suggested that although wheezing symptoms were equally common in Estonia and Sweden, they were less severe in Estonia. More frequent symptoms and a high rate of atopy, BHR and anti-asthmatic medication characterized wheezing children in Sweden. In contrast, BHR, atopy and medication were uncommon among wheezing children in Estonia.
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| 11. |
- Beyer, K., et al.
(author)
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Association and linkage of atopic dermatitis with chromosome 13q12-14 and 5q31-33 markers
- 2000
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In: Journal of Investigative Dermatology. - : Elsevier BV. - 0022-202X .- 1523-1747. ; 115:5, s. 906-908
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Journal article (peer-reviewed)abstract
- Atopic dermatitis is a chronic inflammatory skin disease that affects 10-20% of the population. Linkage of atopy, asthma, allergic rhinitis, and total serum IgE levels to several different chromosomal regions have been described extensively, but little is known about the genetic control of atopic dermatitis. We tested for the association and linkage between atopic dermatitis and five chromosomal regions: 5q31-33, 6p21.3, 12q15-24.1, 13q12-31, and 14q11.2/14q32.1-32.3. Marker analysis was performed in two Caucasian populations: (i) 192 unrelated German children with atopic dermatitis and 59 non-atopic children from a German birth cohort study (MAS '90), parental DNA was tested in 77 of 192 children with atopic dermatitis, (ii) 40 Swedish families with at least one family member with atopic dermatitis selected from the International Study of Asthma and Allergy in Children. Evidence for linkage and allelic association for atopic dermatitis was observed for markers on chromosome 13q12-14 and 5q31-33.
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| 12. |
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| 13. |
- Björkstén, Bengt, et al.
(author)
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Allergy development and the intestinal microflora during the first year of life
- 2001
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In: Journal of Allergy and Clinical Immunology. - 0091-6749 .- 1097-6825. ; 108:4, s. 516-520
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Journal article (peer-reviewed)abstract
- Background: The intestinal microflora is a likely source for the induction of immune deviation in infancy. Objective: The purpose of this study was to prospectively relate the intestinal microflora to allergy development in 2 countries differing with respect to the prevalence of atopic diseases. Methods: Newborn infants were followed prospectively through the first 2 years of life in Estonia (n = 24) and Sweden (n = 20). By that age, 9 Estonian and 9 Swedish infants had developed atopic dermatitis and/or positive skin prick test results. Stool samples were obtained at 5 to 6 days and at 1, 3, 6, and 12 months, and 13 groups of aerobic and anaerobic microorganisms were cultivated through use of standard methods. Results: In comparison with healthy infants, babies who developed allergy were less often colonized with enterococci during the first month of life (72 % vs 96 %, P < .05) and with bifidobacteria during the first year of life (17 % to 39 % vs 42 % to 69 %, P < .05). Furthermore, allergic infants had higher counts of clostridia at 3 months (median value, 10.3 vs 7.2 log(10), P < .05). The prevalence of colonization with Staphylococcus aureus was also higher at 6 months (61 % vs 23 %, P < .05), whereas the counts of Bacteroides were lower at 12 months (9.9 vs 10.6 log(10), P < .05). Conclusion: Differences in the composition of the gut flora between infants who will and infants who will not develop allergy are demonstrable before the development of any clinical manifestations of atopy. Because the observations were made in 2 countries with different standards of living, we believe that our findings could indicate a role for the intestinal microflora in the development of and protection from allergy.
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| 14. |
- Björkstén, Bengt, 1940-
(author)
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Diverse microbial exposure : Consequences for vaccine development
- 2012
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In: Vaccine. - Oxon, United Kingdom : Elsevier. - 0264-410X .- 1873-2518. ; 30:29, s. 4336-4340
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Research review (peer-reviewed)abstract
- Numerous epidemiological studies suggest that there is an inverse relationship between "immunologically mediated diseases of affluence", such as allergy, diabetes and inflammatory bowel disease on one hand and few infections encountered in early childhood, on the other hand. Careful analysis of the epidemiological, clinical and animal studies taken together, however, suggests that the protection is mediated by broad exposure to a wealth of commensal, non-pathogenic microorganisms early in life, rather than by infections. Microbial exposure has little relationship with "hygiene" in the usual meaning of the word and the term "hygiene hypothesis" is therefore misleading. A better term would be "microbial deprivation hypothesis". The suggestion that childhood infections would protect against allergic disease led to unfortunate speculations that vaccinations would increase the risk for allergies and diabetes. Numerous epidemiological studies have therefore been conducted, searching for a possible relationship between various childhood vaccinations on one hand and allergy on the other hand. It is reasonable from these studies to conclude that vaccinations against infectious agents neither significantly increase, nor reduce the likelihood of immunologically mediated diseases. It is established that the postnatal maturation of immune regulation is largely driven by exposure to microbes. Germ free animals manifest excessive immune responses when immunised and they do not develop normal immune regulatory function. The gut is by far the largest source of microbial exposure, as the human gut microbiome contains up to 1014 bacteria, i.e. ten times the number of cells in the human body. Several studies in recent years have shown differences in the composition of the gut microbiota between allergic and non-allergic individuals and between infants living in countries with a low and a high prevalence of immune mediated diseases. The administration of probiotic bacteria to pregnant mothers and postnatal to their infants has immune modulatory effects. So far, however, probiotic bacteria do not seem to significantly enhance immune responses to vaccines. The potential to improve vaccine responses by modifying the gut microbiota in infants and the possibility to employ probiotic bacteria as adjuvants and/or delivery vehicles, is currently explored in several laboratories. Although to date few clinical results have been reported, experimental studies have shown some encouraging results.
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| 15. |
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| 16. |
- Björkstén, Bengt
(author)
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Primary prevention of atopic asthma.
- 2001
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In: Current Opinion in Allergy and Clinical Immunology. - : Ovid Technologies (Wolters Kluwer Health). - 1528-4050 .- 1473-6322. ; 1, s. 545-548
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Journal article (peer-reviewed)
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| 17. |
- Björkstén, Bengt
(author)
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The epidemiology of food allergy
- 2001
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In: Current Opinion in Allergy and Clinical Immunology. - : Ovid Technologies (Wolters Kluwer Health). - 1528-4050 .- 1473-6322. ; 1, s. 225-227
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Journal article (peer-reviewed)
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| 18. |
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| 19. |
- Björkstén, Bengt
(author)
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The intrauterine and postnatal environments
- 1999
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In: Journal of Allergy and Clinical Immunology. - 0091-6749 .- 1097-6825. ; 104:6, s. 1119-1127
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Research review (peer-reviewed)abstract
- Pregnancy is associated with a strong skewing toward T(H)2 cytokine pattern, which enables the survival of the fetus, including fetal allergen-specific immune responses, The postnatal maturation of the immune system which is characterized by the development of a balanced T(H)1/T(H)2 immunity is genetically determined and modified by the environment. The process seems to proceed at a slower rate in atopic than in nonatopic infants. There is a close immunologic interaction between the mother and her offspring through the breast milk. Individual variations in the composition of human milk may el,plain the controversy with regard to the possible allergy-preventive effects of breast-feeding. Recurrent respiratory infections have been suggested to enhance immune deviation. The microbial flora are a more likely source, however, because they are a major driving force in the maturation of the immune system. Changes in its composition, as a consequence of an altered lifestyle and diet, may play a role in the higher prevalence of allergy. So far, primary prevention of allergy has failed. Future studies should therefore focus on factors enhancing immune deviation (ie, "success" factors) rather than on "risk" factors. The intestinal microflora is one of these factors that deserves closer analysis.
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| 20. |
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| 21. |
- Borres, Magnus P., et al.
(author)
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Nasal metachromatic cells in infancy in relation to the appearance of atopic disease during the first 6 years of life
- 1997
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In: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley InterScience. - 0105-4538 .- 1398-9995. ; 52:7, s. 770-774
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Journal article (peer-reviewed)abstract
- The relationship between the appearance of nasal metachromatic cells (basophils and mast cells) during the first 18 months of life and the development of respiratory and other allergic diseases up to 6 years of age was studied prospectively in 67 children. Follow-up was done at 3, 6, 9, and 18 months and 6 years. Of the 31 children who had detectable metachromatic cells in the nasal mucosa during infancy, 18 had atopic manifestations at 6 years (58%), two were probably atopic (6%), and 11 (36%) were nonatopic. The corresponding numbers for the 33 children without detectable metachromatic cells during infancy were 10 atopic (30%), two probably atopic (6%), and 21 nonatopic (64%) at 6 years (P<0.05). Children having detectable nasal metachromatic cells at every examination were more often allergic than children with no detectable cells at any time during the 6-year follow-up period (P<0.05). In contrast, nasal metachromatic cells were equally commonly demonstrated at 6 years in children with and without current atopic manifestations. We conclude that metachromatic cells appear at an earlier age in the nasal mucosa of atopic than nonatopic infants. The observation further supports the existence of a primary immunologic abnormality in atopic patients as related to allergic inflammatory responses. The diagnostic efficacy of this marker was too low, however, to be clinically useful as a predictor of allergy.
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| 22. |
- Bråbäck, Lennart, et al.
(author)
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Atopic sensitization and respiratory symptoms among Polish and Swedish school children
- 1994
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In: Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology. - 0954-7894. ; 24:9, s. 826-835
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Journal article (peer-reviewed)abstract
- Allergic sensitization and symptoms from the airways in relation to air pollution were compared in 10-12-year-old school children (n = 1113) from urban Konin in central Poland and both urban and rural parts of Sundsvall in northern Sweden. The measurements included parental questionnaires, skin-prick tests and serial peak flow measurements during 2 weeks with simultaneous monitoring of outdoor air pollutants. The skin-prick test technique was validated by IgE antibody determinations. The levels of common industrial pollutants, SO2 and smoke particles were much higher in Konin than in urban Sundsvall and the levels of NO2 were similar. Various respiratory symptoms were more often reported among school children in Konin (except for wheezing and diagnosed asthma). Multiple logistic regression analyses yielded the following increased odds ratios for children in Konin as compared with the reference group (rural Sundsvall): chest tightness and breathlessness 3.48 (95% confidence interval 2.08-5.82), exercise-induced coughing attacks 3.69 (95% confidence interval 1.68-8.10), recurrent episodes of common cold 2.79 (95% confidence interval 1.53-5.09) and prolonged cough 4.89 (95% confidence interval 2.59-9.23). In contrast, as compared with rural Sundsvall, the adjusted odds ratio for a positive skin-prick test was decreased in Konin, but increased in urban Sundsvall, 0.58 (95% confidence interval 0.37-0.91) and 1.67 (95% confidence interval 1.15-2.42) respectively. The study confirms that living in urban, as compared with rural areas, is associated with an increased prevalence of respiratory symptoms and sensitization to allergens. These differences could be explained by air pollution. Respiratory symptoms were more common in a similar urban group of Polish children who were exposed to even higher levels of air pollution. These children, however, had a much lower prevalence of sensitization to allergens, as compared with the Swedish children. This indicates that differences in lifestyle and standard of living between western Europe and a former socialist country influences the prevalence of atopy.
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| 23. |
- Bråbäck, Lennart, et al.
(author)
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Atopy among schoolchildren in northern and southern Sweden in relation to pet ownership and early life events
- 2001
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 12:1
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Journal article (peer-reviewed)abstract
- Studies have suggested a higher prevalence of asthma and allergies in northern, as compared to southern. Scandinavia. The aim of this study was to evaluate regional differences in atopy in relation to pet ownership and certain early life events among schoolchildren. (n=2108) aged 10-11 years from Link÷ping in southern Sweden and ╓stersund in northern Sweden. The parents completed a questionnaire, comprising questions on home environment, heredity, socio-economic conditions, and the core questions on symptoms from the International Study of Asthma and Allergies in Childhood. The children were skin-prick tested to eight common inhalant allergens. Information on maternal smoking habits, gestational age, and anthropometric measures were obtained from the Swedish Medical Birth Registry. The prevalence of atopic symptoms and sensitization to pollen were similar in ╓stersund and in Link÷ping. A higher prevalence of sensitization to animal dander among children in ╓stersund could be linked to a higher occurrence of pets in the community. Current cat ownership was related to less sensitivity to cat allergen but only in children with an atopic heredity. Ponderal index >30 kg/m3 was related to an increased risk of atopic sensitization, both in Link÷ping (adjusted odds ratio 2.1, 95% confidence interval 1.1-4.0) and in ╓stersund (adjusted odds ratio 2.0, 95% confidence interval 1.1-3.5). Maternal smoking during pregnancy was related to an increased risk of atopic sensitization among children in Link÷ping, whereas current smoking was associated with a decreased risk of sensitization in -stersund. In conclusion, we demonstrated that a high occurrence of pets in the community was associated with sensitization, whereas atopic symptoms were essentially unaffected. This study has also suggested an association between body size at birth and atopic sensitization at 10-11 years of age.
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| 24. |
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| 25. |
- Böttcher (Fagerås), Malin, et al.
(author)
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Endotoxin levels in Estonian and Swedish house dust and atopy in infancy
- 2003
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In: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 33:3, s. 295-300
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Journal article (peer-reviewed)abstract
- Background Immune responses, including those to allergens, may be T helper (Th)2 skewed in newborns. In order to redress the fetal Th1/Th2 imbalance, Th1-stimulating factors, such as bacterial endotoxin, may be required. The increasing prevalence and severity of atopic diseases in industrialized countries, which are in marked contrast with the low prevalence of allergy among children in the formerly socialist countries of Europe, have been suggested to be caused by a reduced microbial stimulation.Aim To relate the endotoxin levels in house dust from two countries with a low (Estonia) and a high (Sweden) prevalence of allergy to the development of atopic disease and sensitization in the children during the first 2 years of life.Methods The study included 108 children from Tartu, Estonia and 111 children from Linköping, Sweden. Skin prick tests were performed at 3, 6, 12 and 24 months of age, and questionnaires were distributed to the families. At 24 months, a paediatrician examined the children. Dust samples were collected from mattresses and carpets and the endotoxin concentration was determined by a chromogenic Limulus assay.Results The endotoxin levels were higher in Estonian than in Swedish house dust (median levels 29 (range 0.25–280) and 14 (range 0.25–99) EU/mg dust, respectively, P < 0.001). Furthermore, the levels were inversely related to the development of atopic disease and sensitization in the Swedish, but not in the Estonian, children.Conclusions The low prevalence of atopic disease in Estonia may, at least in part, be related to the high endotoxin levels in this country. The findings support that high levels of endotoxin, or other bacterial products with Th1-stimulating properties, might protect children from developing atopic disease.
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| 26. |
- Böttcher, Malin, et al.
(author)
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Chemoattractant factors in breast milk from allergic and nonallergic mothers
- 2000
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In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 47:5, s. 592-597
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Journal article (peer-reviewed)abstract
- The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. Recently, we showed that allergic mothers had higher concentrations of IL-4 and lower concentrations of ovalbumin-specific IgA in their breast milk than nonallergic mothers. The aim of this study was to investigate the concentrations of chemokines and cytokines that are chemotactic to cells involved in allergic reactions in breast milk from allergic and nonallergic mothers. Cytokine and chemokine concentrations were determined with ELISA in colostrum and mature milk samples from 23 mothers with and 25 mothers without atopic symptoms. IL-8 was detected in all milk samples. RANTES (regulated on activation, normal T cell expressed and secreted), eotaxin, and IL-16 were detected in 50%, 76%, and 48%, respectively, in colostrum and less commonly in mature milk. Macrophage inflammatory protein-1α, however, could not be detected in any of the samples. The concentrations of IL-8 and RANTES were higher in breast milk from allergic, compared with nonallergic, mothers. In conclusion, the presence of chemoattractant factors in breast milk may be responsible for the traffic of leukocytes from the maternal circulation to the breast milk. The higher concentrations of RANTES and IL-8 in allergic mothers may partly explain the controversy regarding the protective effect of breast-feeding against the development of allergy by stronger chemotaxis and activation of cells involved in allergic diseases, and possibly by elevated IgE production.
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| 27. |
- Böttcher, Malin, 1969-, et al.
(author)
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Cytokine, chemokine and secretory IgA levels in human milk in relation to atopic disease and IgA production in infants
- 2003
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 14:1, s. 35-41
-
Journal article (peer-reviewed)abstract
- The relationship between breast-feeding, IgA production and development of atopic disease in children is a matter of controversy. Some of this controversy might be due to individual differences in the composition of breast milk. The aim of this study was to relate the levels of cytokines, chemokines and secretory (S)-IgA antibodies in breast milk to the development of atopic manifestation and salivary IgA production in infants. Cytokine, chemokine and SIgA levels, as measured with enzyme-linked immunosorbent assay (ELISA), in colostrum and mature milk were analyzed in relation to the development of positive skin-prick tests (SPT), allergic symptoms and salivary IgA antibody production during the first 2 years of life in 53 infants. There was no association between levels of IL-4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-β1, -β2, RANTES, eotaxin or SIgA levels in the breast milk with either SPT-positivity, development of allergic symptoms or salivary IgA levels during the first 2 years of life in the infants. Thus, differences in the composition of cytokines, chemokines and SIgA in breast milk did not, to any major degree, affect the development of a positive SPT, atopic symptoms, nor salivary IgA antibody production during the first 2 years of life.
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| 28. |
- Böttcher, Malin, 1969-, et al.
(author)
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Cytokines in breast milk from allergic and nonallergic mothers
- 2000
-
In: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 47:1, s. 157-162
-
Journal article (peer-reviewed)abstract
- The allergy-preventing effect of breast-feeding remains controversial, possibly because of individual variations in the composition of the breast milk. The aim of this study was to investigate the concentrations of cytokines involved in allergic reactions and IgA antibody production in breast milk from allergic and nonallergic mothers. The cytokine concentrations were determined in colostrum and 1-mo milk samples from 24 mothers with, and 25 mothers without, atopic symptoms, using commercial ELISA kits. The immunosuppressive cytokine transforming growth factor-β was predominant and was detectable in all milk samples. IL-6 was detected in the majority of colostral and mature milk samples, whereas the other cytokines were less commonly detected. The concentrations of IL-6, IL-10, and transforming growth factor-β, which are all involved in IgA synthesis, correlated with each other and with total IgA concentrations in colostrum. The concentrations of IL-4 were higher in colostrum from allergic than nonallergic mothers, and similar trends were seen for IL-5 and IL-13. In conclusion, transforming growth factor-β and IL-6 were the predominant cytokines in human milk. The correlation between the concentrations of cytokines involved in IgA synthesis, i.e. IL-10, IL-6, and transforming growth factor-β, may explain the stimulatory effect on IgA production in breast-fed babies. Varying concentrations of IL-4, IL-5, and IL-13 may explain some of the controversy regarding the possible allergy-preventive effect of breast-feeding.
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| 29. |
- Böttcher, Malin, 1969-, et al.
(author)
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Human milk polyunsaturated long-chain fatty acids and secretory immunoglobulin A antibodies and early childhood allergy
- 2000
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 11:1, s. 29-39
-
Journal article (peer-reviewed)abstract
- The possible protective effect of breast milk against atopic manifestations in infancy, i.e. atopic eczema and food allergy, has been controversial for the last decades. Besides the methodological problems, differences in the composition of human milk could explain these controversies. The aim of this study was to investigate the composition of polyunsaturated fatty acids (PUFA) and secretory immunoglobulin A (S-IgA) levels to food proteins (ovalbumin and ▀-lactoglobulin) and an inhalant allergen (cat) in milk from mothers of allergic and non-allergic children. Blood samples were obtained at birth and at 3 months from 120 children. Skin prick tests were performed at 6, 12 and 18 months, and the development of atopic diseases was assessed in the children. Breast milk samples were collected from their mothers at birth and monthly during the lactation period. Milk PUFA composition was measured by gas chromatography, and enzyme-linked immunosorbent assay (ELISA) was used to measure total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA. Allergic disease developed in 44/120 children (22/63 children of allergic mothers and 22/57 children of non-allergic mothers). Lower levels of eicosapentaenoic acid, C20:5 n-3 (EPA), docosapentaenoic acid C22:5 n-3 (DPA), and docosatetraenoic acid C22:4 n-6 (DHA) (p < 0.05 for all) were found in mature milk from mothers of allergic as compared to milk from mothers of non-allergic children. The total n-6 : total n-3 and the arachidonic acid, C20:4 n-6 (AA) : EPA ratios were significantly lower in transitional and mature milk from mothers of allergic children, as compared to milk from mothers of non-allergic children. The PUFA levels in serum of allergic and non-allergic children were largely similar, except for higher levels of C22:4 n-6 and C22:5 n-6 (p < 0.05 for both) and a higher AA:EPA ratio in serum phospholipids in the former group (p < 0.05). Changes in the levels of milk PUFA were reflected in changes in PUFA serum phospholipids, particularly for the n-6 PUFA. The AA:EPA ratio in maternal milk was related, however, to the AA:EPA only in serum from non-allergic children, while this was not the case in allergic children. The levels of total S-IgA, anti-cat S-IgA, anti-ovalbumin S-IgA, and anti-▀-lactoglobulin S-IgA in milk from mothers of allergic, as compared to non-allergic, children were similar through the first 3 months of lactation. Low levels of n-3 PUFA in human milk, and particularly a high AA:EPA ratio in maternal milk and serum phospholipids in the infants, were related to the development of symptoms of allergic disease at 18 months of age. The milk PUFA composition influenced the composition of PUFA in serum phospholipids of the children. We also showed that the lower levels of colostral anti-ovalbumin S-IgA and lower total S-IgA in mature milk from atopic mothers did not influence the development of allergic disease in the children up to 18 months of age. The findings indicate that low a-linolenic acid, C18:3 n-3 (LNA) and n-3 long-chain polyunsaturated fatty acids (LCP) 20-22 carbon chains, but not the levels of S-IgA antibodies to allergens, are related to the development of atopy in children.
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| 30. |
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| 31. |
- Böttcher, Malin, et al.
(author)
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Microflora-associated characteristics in faeces from allergic and nonallergic infants
- 2000
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In: Clinical and Experimental Allergy. - 0954-7894 .- 1365-2222. ; 30:11, s. 1590-1596
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Journal article (peer-reviewed)abstract
- Background The prevalence of allergic diseases has increased particularly over the past 30-40 years. A reduced microbial stimulation during infancy may result in a development of a disturbed balance between Th1- and Th2-like immunity. The gut flora is, quantitatively, the most important source for such stimulation. Objective The aim of the study was to compare the gut microbial flora in 25 allergic and 47 nonallergic 13-month-old infants (range 11-18), through analysing microflora-associated biochemical markers in faeces. Methods Microflora associated characteristics (MACs) were assessed by determining the concentrations of eight different short chain fatty acids and the conversion of cholesterol to coprostanol by gas chromatography. Faecal tryptic activity was analysed spectrophotometrically. Results The allergic infants had lower levels of propionic, i-butyric, butyric, i-valeric and valeric acid. In contrast, they had higher levels of the rarely detected i-caproic acid, which has been associated with the presence of Clostridium difficile. Furthermore, the allergic infants had higher relative distribution of acetic and i-caproic acid. None of the other parameters differed between the groups. Conclusion The results demonstrate differences in the MACs between allergic and nonallergic infants, indicating differences in the composition of the gut flora. that may disturb the development of a normal Th1-/Th2-balance in allergic children.
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| 32. |
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| 33. |
- Böttcher, Malin, 1969-, et al.
(author)
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Total and allergen-specific immunoglobulin a levels in saliva in relation to the development of allergy in infants up to 2 years of age
- 2002
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 32:9, s. 1293-1298
-
Journal article (peer-reviewed)abstract
- Background: The association between salivary IgA levels and development of allergy is controversial and the employed methodology has been questioned. Objective: The aim of the study was to relate the levels of total IgA, SIgA and allergen-specific IgA antibodies in saliva to the development of allergy in infants during the first 2 years of life. Methods: Saliva samples from 80 infants participating in a prospective study regarding the development of allergy were collected at 3 or 6, and 12 and 24 months of age. Total IgA, SIgA and Fel d 1 and ▀-lactoglobulin specific IgA levels were analysed with ELISA. Results: The levels of total IgA and SIgA increased with age. The number of samples with detectable IgA to Fel d 1 tended to increase with age, whereas the opposite was observed for IgA to ▀-lactoglobulin. Infants who developed allergy tended to have higher levels of total IgA, and allergen-specific IgA was more commonly detected than in non-allergic children. In contrast, non-allergic children tended to have higher levels of SIgA. Furthermore, the levels of SIgA were higher in sensitized infants with no allergic symptoms than in sensitized children with symptoms. Infants with allergic parents had lower SIgA levels than infants without. Direct exposure to cat and cow's milk did not influence the levels of allergen-specific IgA levels, nor was there any association between breast-feeding and IgA production. Conclusion: The kinetics of food and inhalant allergen-specific IgA in saliva during the first 2 years of life is similar to what has earlier been shown for IgG in serum. Development of allergy tended to be associated with high levels of total and allergen-specific IgA antibodies, but low levels of SIgA. Furthermore, high levels of SIgA seemed to protect sensitized children from developing allergic symptoms during the first 2 years of life, supporting a possible protective role of SIgA against development of allergy.
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| 34. |
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| 35. |
- Casas, Rosaura, 1954-, et al.
(author)
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Cat allergen-induced cytokine secretion and Fel d 1–immunoglobulin G immune complexes in cord blood
- 2004
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 34:4, s. 591-596
-
Journal article (peer-reviewed)abstract
- Background We have recently obtained evidence for the presence of immune complexes (IC) in cord blood from allergic and non-allergic mothers. Such complexes could conceivably provide the fetus with the initial trigger for the priming of the T cell system already in utero.Objective To relate the presence of Fel d 1–IgG IC to T cell cytokine production in cord blood mononuclear cells (CBMCs) after stimulation with cat allergen.Methods CBMC obtained from babies of 15 allergic and 22 non-allergic mothers were cultured in the presence of cat allergen. The production of IFN-γ, IL-5, IL-10 and IL-13 was determined by ELISA. Furthermore, IgG1 and IgG4 antibodies to cat allergen in cord blood samples were measured by ELISA. A more sensitive ELISA was used to measure Fel d 1–IgG IC.Results The prevalence and levels of IC were similar in cord blood from children of allergic and non-allergic mothers. The production of IL-5, IL-10. IL-13 and IFN-γ by CBMC was not influenced by maternal atopy, but IFN-γ was less commonly detected in samples with IC. There was no association between the presence of IC and any other cytokines. The levels of IgG1 and IgG4 antibodies were similar in both groups, and tended to be associated with the presence of IC.Conclusion Immune complexes in cord blood may represent a normal mechanism for inducing primary immune responses, as the responses in babies from allergic and non-allergic mothers were largely similar. Low levels of IFN-γ seems to be related with the presence of IC in cord blood.
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| 36. |
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| 37. |
- Casas, Rosaura, 1954-, et al.
(author)
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Detection of Fel d 1–immunoglobulin G immune complexes in cord blood and sera from allergic and non-allergic mothers
- 2001
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In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 12:2, s. 59-64
-
Journal article (peer-reviewed)abstract
- It is an established fact that T-cell responses of fetal origin to inhalant allergens are present in most cord blood samples. These immune responses could be explained by trans-placental passage of peptides, either as free antigens or in complexes with immunoglobulin G (IgG), providing the fetus with a trigger for priming the T-cell system already present in utero. The aim of this study was to investigate the presence of the major cat allergen, Fel d 1, in complexes with IgG in cord blood and maternal sera. Serum samples from 75 mothers (38 allergic, 37 non-allergic), and cord blood from their infants, were investigated for the presence of Fel d 1–IgG immune complexes (ICs) by using an amplified enzyme-linked immunosorbent assay (ELISA). Three monoclonal antibodies to Fel d 1 were used for coating. The specificity of the method was confirmed by inhibition experiments. ICs of Fel d 1–IgG were detected in the sera of 45% allergic and 49% non-allergic mothers, and in, respectively, 34% and 41% of their infants. Therefore, neither the prevalence nor the level of ICs were affected by maternal allergy. Low levels of trans-placentally transferred ICs can provide the fetus with a signal for the priming of T-cell responses to inhalant allergens. However, this is not necessarily related to allergic disease.
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| 38. |
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| 39. |
- Casas, Rosaura, 1954-, et al.
(author)
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Detection of IgA antibodies to cat, β-lactoglobulin, and ovalbumin allergens in human milk
- 2000
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 105:6 part 1, s. 1236-1240
-
Journal article (peer-reviewed)abstract
- Background: The relationship between the development of allergy during infancy and breast-feeding remains controversial. This controversy may be due to individual variations in the composition of human milk. Antibodies to food antigens to which the mother is commonly exposed are present in the milk, but their relationship to allergy is still unknown. IgA antibodies to inhalant allergens have not been previously detected.Objective: Our purpose was to analyze secretory IgA antibody levels to cat, β-lactoglobulin, and ovalbumin allergens in colostrum and mature milk in relation to maternal allergy.Methods: Colostrum and samples of mature milk were obtained after 1 and 3 months of lactation from 53 nursing mothers (17 allergic and 36 nonallergic mothers) and were analyzed for total secretory IgA levels by ELISA and secretory IgA antibodies to cat, β-lactoglobulin, and ovalbumin by an enzyme-amplified ELISA. The specificity of the assays was confirmed by inhibition experiments.Results: Secretory IgA to cat, β-lactoglobulin, and ovalbumin allergens were detected in colostrum as well as mature milk. The levels of secretory IgA to ovalbumin were lower in colostrum from allergic mothers with P = .016, whereas the levels to β-lactoglobulin and cat were similar in the 2 groups. IgA antibodies to ovalbumin were detected in 94% of the colostrum samples from allergic and in all samples from nonallergic mothers, in 82% and 96%, respectively at 1 month, and 53% and 65% at 3 months. Fewer samples had detectable secretory IgA antibodies to β-lactoglobulin than to ovalbumin and cat, and only 33% and 10% of the samples from the allergic and nonallergic mothers, respectively, remained positive at 3 months. All the allergic mothers had detectable IgA to cat in colostrum, whereas 83% and 73% of the samples were positive at 1 and 3 months. The corresponding numbers were 93%, 81%, and 81% in the nonallergic mothers (not significant).Conclusion: Even a low level of exposure of the mucosa (eg, by inhalant allergens) can induce antibody secretion into the milk, both in allergic and nonallergic mothers. (J Allergy Clin Immunol 2000;105:1236-40.)
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| 40. |
- Casas, Rosaura, et al.
(author)
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Presence of Fel d 1 - IgE immune complexes in sera from cat allergic individuals
-
Other publication (other academic/artistic)abstract
- Background: We have recently reported the presence of immune complexes (IC) with the inhalant allergen Fel d I, in serum samples from cat allergic children. It was not entirely excluded however that these findings were due to the presence of human antibodies against cat serum albumin. The objective of this work was to confirm the presence of the major cat allergen Fel d I in complexes with IgE and to assess the specificity of the human IgE antibodies to cat allergen.Methods: Serum samples from 27 cat allergic children were investigated. For the detection of Fel d 1-IgE IC, a chemiluminescent immunoassay was modified by coupling an anti-Fel d I monoclonal antibody to paramagnetic particles. Levels of IgE antibodies to cat allergens were determined by chemiluminiscense and RAST, and IgG4 antibody levels by RAST.Results: Fifteen samples contained IgE-Fel d I IC. The levels of IC correlated with the levels of specific lgE antibodies to cat allergen correlated (r=0.48; p<0.05). All the samples of the 27 cat allergic children contained IgE and IgG4 antibodies against cat allergen, while IgE and IgG4 antibodies to cat serum were only demonstrated in 4/27 (14 %) and 6/27 (22%) samples respectively. Conclusions: Immune complexes with the major cat allergen, Fel d I, were commonly present in serum samples from cat allergic children.
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| 41. |
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| 42. |
- Duchen, Karel, 1961-, et al.
(author)
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Polyunsaturated n-3 fatty acids and the development of atopic disease
- 2001
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In: Lipids. - 0024-4201 .- 1558-9307. ; 36:9, s. 1033-1042
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Journal article (peer-reviewed)abstract
- The relationship between polyunsaturated longchain fatty acids and atopy has been discussed for decades. Higher levels of the essential fatty acids linoleic acid and a-linolenic acid and lower levels of their longer metabolites in plasma phospholipids of atopic as compared to nonatopic individuals have been reported by several, but not all, studies. Largely similar findings have been reported in studies of cell membranes from immunological cells from atopics and nonatopics despite differences in methodology, study groups, and definitions of atopy. An imbalance in the metabolism of the n-6 fatty acids, particularly arachidonic acid and dihomo-?-linolenic acid, leading to an inappropriate synthesis of prostaglandin (PG) E2 and PGE1 was hypothesized early on but has not been corroborated. The fatty acid composition of human milk is dependent on the time of lactation not only during a breast meal but also the time of the day and the period of lactation. This explains the discrepancies in reported findings regarding the relationship between milk fatty acids and atopic disease in the mother. Prospective studies show disturbances in both the n-6 and n-3 fatty acid composition between milk from atopic and nonatopic mothers. Only the composition of long-chain polyunsaturated n-3 fatty acids was related to atopic development in the children, however. A relationship between lower levels of n-3 fatty acids, particularly eicosapentaenoic acid (20:5 n-3), and early development of atopic disease is hypothesized.
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| 43. |
- Dzidic, Majda, et al.
(author)
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Aberrant IgA responses to the gut microbiota during infancy precede asthma and allergy development
- 2017
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In: Journal of Allergy and Clinical Immunology. - : MOSBY-ELSEVIER. - 0091-6749 .- 1097-6825. ; 139:3, s. 1017-
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Journal article (peer-reviewed)abstract
- Background: Although a reduced gut microbiota diversity and low mucosal total IgA levels in infancy have been associated with allergy development, IgA responses to the gut microbiota have not yet been studied. Objective: We sought to determine the proportions of IgA coating together with the characterization of the dominant bacteria, bound to IgA or not, in infant stool samples in relation to allergy development. Methods: A combination of flow cytometric cell sorting and deep sequencing of the 16S rDNA gene was used to characterize the bacterial recognition patterns by IgA in stool samples collected at 1 and 12 months of age from children staying healthy or having allergic symptoms up to 7 years of age. Results: The children with allergic manifestations, particularly asthma, during childhood had a lower proportion of IgA bound to fecal bacteria at 12months of age compared with healthy children. These alterations cannot be attributed to differences in IgA levels or bacterial load between the 2 groups. Moreover, the bacterial targets of early IgA responses (including coating of the Bacteroides genus), as well as IgA recognition patterns, differed between healthy children and children with allergic manifestations. Altered IgA recognition patterns in children with allergy were observed already at 1 month of age, when the IgA antibodies are predominantly maternally derived in breast-fed children. Conclusion: An aberrant IgAresponsiveness to the gutmicrobiota during infancy precedes asthma and allergy development, possibly indicating an impaired mucosal barrier function in allergic children.
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| 44. |
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| 45. |
- Fagerås Böttcher, Malin, et al.
(author)
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A TLR4 polymorphism is associated with asthma and reduced lipopolysaccharide-induced interleukin-12(p70) responses in Swedish children
- 2004
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In: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 114:3, s. 561-567
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Journal article (peer-reviewed)abstract
- Background Bacterial signals play an important role in the maturation of the immune system. Polymorphisms in genes coding for receptors to bacterial components can alter the immune responsiveness of the host to microbial agents and may indicate the development of aberrant immune responses that are associated with immune-mediated diseases such as atopic diseases. Objective The study's objective was to investigate the relationship between TLR4 and CD14 gene polymorphisms, the LPS responsiveness of PBMCs, and the presence of asthma and allergic rhinoconjunctivitis in children. Methods The TLR4 (Asp299Gly) and CD14/−159 polymorphisms were determined in 115 Swedish children aged 8 and 14 years. LPS-induced IL-12(p70), IL-10, and IFN-γ responses of PBMCs from 69 of the children were analyzed by means of ELISA. The levels of soluble CD14 in serum samples were analyzed by means of ELISA, and the total IgE levels were analyzed by means of UniCAP Total IgE (Pharmacia Diagnostics, Uppsala, Sweden). Results Decreased LPS-induced IL-12(p70) and IL-10 responses were associated with the TLR4 (Asp299Gly) polymorphism and independently with asthma, especially atopic asthma. The TLR4 (Asp299Gly) polymorphism was associated with a 4-fold higher prevalence of asthma in school-aged children (adjusted odds ratio 4.5, 95% CI 1.1-17.4) but not to allergic rhinoconjunctivitis. Conclusion A TLR4 polymorphism modifies innate immune responses in children and may be an important determinant for the development of asthma. This may influence the outcome of intervention studies that use microbial stimuli as immune modulators.
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| 46. |
- Fagerås Böttcher, Malin, 1969-, et al.
(author)
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Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish children
- 2006
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 36:5, s. 619-628
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Journal article (peer-reviewed)abstract
- Background The prevalence of atopic disease among children in the formerly socialist countries in Europe, with a life style similar to that prevailing in Western Europe 30–40 years ago, is low, whereas there has been a pronounced increase in industrialized countries over the last decades. The environment during infancy influences the risk of developing allergy for many years, perhaps even for life.Objective To investigate the development of allergen-specific cytokine responses during the first 2 years of life in two geographically adjacent countries with marked differences in living conditions and incidence of atopic diseases, i.e. Estonia and Sweden.Methods The development of immune responses to food (β-lactoglobulin (BLG) and ovalbumin (OVA)) and inhalant (cat and birch) allergens was studied from birth up to the age of 2 years in 30 Estonian and 76 Swedish infants. Clinical investigation and skin prick tests were performed and blood samples were obtained at birth and at 3, 6, 12 and 24 months.Results The levels of IL-5, IL-10 and IL-13 secreted by peripheral blood mononuclear cells stimulated with BLG, OVA and cat allergen in Estonian and Swedish infants declined during the first 3 months of life. All cytokines then progressively increased in the Swedish infants, indicating the replacement of non-specifically responding immature cord blood T cells with specific T memory cells, which are primed postnatally. The resurgence of allergen-specific responses in the Estonian infants was less marked. These differences were particularly notable for birch-specific T cell responses, which correlated with development of atopic disease in the Swedish children.Conclusions The development of specific T cell memory to food and inhalant allergens during the first 2 years of life differs between infants living in Sweden and Estonia, and mirrors the disparate patterns of expression of allergic disease which subsequently develops in the respective populations.
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| 47. |
- Fagerås Böttcher, Malin, 1969-, et al.
(author)
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Cytokines in breast milk from allergic and nonallergic mothers
- 1999
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In: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 118:2-4, s. 319-320
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Journal article (peer-reviewed)abstract
- Sorry, there is no abstract. Read the first few lines of the text instead!The allergy–preventing effect of breast–feeding is controversial [1, 2]. This may be due to individual variations of the composition of human milk. Allergy is associated with a bias to production of cytokines involved in IgE synthesis, e.g. IL–4 and IL–13 [3] and the eosinophil chemotactic [4] and survival [5] factor IL–5. In contrast, IFN–=γ, which inhibits IgE synthesis [6], is downregulated [7]. Cytokines involved in IgA production, IL–6, IL–10 and TGF–β [8, 9] have also been proposed to be involved in IgE synthesis [10, 11, 12].
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| 48. |
- Fagerås-Böttcher, Malin, 1969-, et al.
(author)
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Immune responses to birch in young children during their first 7 years of life
- 2002
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In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 57, s. 43-43
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Journal article (peer-reviewed)abstract
- Background The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life.Objective To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life.Methods Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch-induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic LiteTM and birch-induced mononuclear cell proliferation with 3H-thymidine incorporation.Results Birch-induced IFN-γ and IL-10 production increased with age, both in atopic and non-atopic children, while birch-induced IL-13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL-4 and IL-5 production and IL-9 mRNA expression, as well as Th2-associated IgG4 responses. Transient Th2-like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children.Conclusions Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2-like response is down-regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen.
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| 49. |
- Fagerås Böttcher, Malin, et al.
(author)
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Low breast milk TGF-beta2 is induced by Lactobacillus reuteri supplementation and associates with reduced risk of sensitization during infancy
- 2008
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In: Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. - : Wiley. - 1399-3038. ; 19:6, s. 497-504
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Journal article (peer-reviewed)abstract
- The immunological composition of breast milk differs between mothers. The reasons for these differences and the consequences for the breast-fed infants are poorly understood. The aim of this study was to evaluate the effect of probiotic Lactobacillus reuteri supplementation on the immunological composition of breast milk in relation to sensitization and eczema in the babies. Total IgA, secretory IgA (SIgA), TGF-beta1, TGF-beta2, IL-10, TNF, soluble CD14 (sCD14), and Na/K ratios were analyzed in colostrum and mature milk obtained from women treated with L. reuteri (n = 54) or placebo (n = 55) from gestational week 36 until delivery. Bacteriological analyses of L. reuteri were performed in faecal samples of the mothers. The infants were followed prospectively for 2 yr regarding development of eczema and sensitization as defined by a positive skin prick test and/or circulating allergen-specific IgE antibodies at 6, 12, and 24 months of age. Supplementation of L. reuteri during pregnancy was associated with low levels of TGF-beta2 and slightly increased levels of IL-10 in colostrum. For TGF-beta2, this association was most pronounced in mothers with detectable L. reuteri in faeces. Infants receiving breast milk with low levels of TGF-beta2 were less likely to become sensitized during their first 2 yr of life. A similar trend was observed for development of IgE-associated eczema. The levels of total IgA, SIgA, TGF-beta1, TNF, sCD14, and Na/K ratios in breast milk were not affected by the intake of L. reuteri. None of these parameters correlated with sensitization or development of eczema in the infant, except for high Na/K ratios that associated with increased risk of sensitization. Supplementation with L. reuteri during late pregnancy reduces breast milk levels of TGF-beta2, and low levels of this cytokine are associated with less sensitization and possibly less IgE-associated eczema in breast-fed infants.
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- Fagerås Böttcher, Malin, et al.
(author)
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Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children
- 2011
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In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 70:6, s. 572-577
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Journal article (peer-reviewed)abstract
- It is unknown why allergic symptoms do not develop in all sensitized children. We analyzed prospectively the postnatal secretory IgA (SIgA) development and whether high SIgA levels would protect sensitized infants from developing allergic symptoms. Salivary total IgA and SIgA levels were determined by ELISA, and allergy development was investigated at 3, 6, and 12 mo and at 2 and 5 y in two birth cohorts in Estonia (n = 110) and Sweden (n = 91), two geographically adjacent countries with different living conditions and allergy incidence. Total and SIgA levels increased with age, reaching adult levels at the age of 5. Virtually, all salivary IgA in Estonian children was in the secretory form, while a major part of IgA in Swedish saliva lacked the secretory component up to 2 y of age. In Sweden, high levels of salivary IgA without secretory component correlated inversely with house dust endotoxin levels. High SIgA levels were associated with less development of allergic symptoms in sensitized Swedish children. In conclusion, postnatal maturation of the salivary SIgA system proceeds markedly slower in Swedish than Estonian children, possibly as a consequence of low microbial pressure. SIgA may limit allergy-mediated tissue damage at mucosal surfaces in sensitized individuals.
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