| 1. |
- Abrahamsson, Thomas R, 1968-, et al.
(författare)
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Probiotics in prevention of IgE-associated eczema : a double-blind, randomized, placebo-controlled trial
- 2007
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 119:5, s. 1174-1180
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Benn, CS, et al.
(författare)
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Mammary epithelial paracellular permeability in atopic and non-atopic mothers versus childhood atopy
- 2004
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 15:2, s. 123-126
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Tidskriftsartikel (refereegranskat)abstract
- Sodium/potassium (Na/K) ratios are considered to be a marker of mammary epithelial paracellular permeability. The aim of the present study was to investigate the association between maternal atopy and Na/K ratios in breast milk and the association between Na/K ratios in breast milk and the development of atopy in the offspring. Early and mature milk samples were obtained from 30 atopic and 43 non-atopic women. We found no differences in the Na/K ratios between atopic and non-atopic women. At 18 months of age, 22 (30%) of the children had a positive skin prick test (SPT) and 26 (36%) had symptoms of atopic diseases. Overall, high levels of Na/K compared with low and slightly raised levels of Na/K in the maternal milk tended to be associated with a positive SPT and atopic disease. However, if the mother was atopic, high levels of Na/K in early or mature milk were associated with a significantly increased risk of a positive SPT or atopic disease in the offspring [RR = 4.8 (1.9-12)] whereas no such association was observed in non-atopic mothers [RR = 0.8 (0.4-1.7), p for interaction = 0.001]. Thus, high Na/K levels in the breast milk may be associated with the development of atopy and atopic diseases in the offspring of atopic mothers.
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| 3. |
- Böttcher (Fagerås), Malin, et al.
(författare)
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Endotoxin levels in Estonian and Swedish house dust and atopy in infancy
- 2003
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 1365-2222 .- 0954-7894. ; 33:3, s. 295-300
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Tidskriftsartikel (refereegranskat)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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| 4. |
- Fagerås Böttcher, Malin, et al.
(författare)
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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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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 114:3, s. 561-567
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Tidskriftsartikel (refereegranskat)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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| 5. |
- Fagerås Böttcher, Malin, 1969-, et al.
(författare)
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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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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 36:5, s. 619-628
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Tidskriftsartikel (refereegranskat)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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| 6. |
- Fagerås Böttcher, Malin, 1969-, et al.
(författare)
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Cytokines in breast milk from allergic and nonallergic mothers
- 1999
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Ingår i: International Archives of Allergy and Immunology. - : S. Karger AG. - 1018-2438 .- 1423-0097. ; 118:2-4, s. 319-320
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Tidskriftsartikel (refereegranskat)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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| 7. |
- Fagerås-Böttcher, Malin, 1969-, et al.
(författare)
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Immune responses to birch in young children during their first 7 years of life
- 2002
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Ingår i: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 57, s. 43-43
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Fagerås-Böttcher, Malin, 1969-
(författare)
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Immunological factors in breast milk in relation to allergy in mother and child
- 2002
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The allergy preventive effect of breast-feeding against the development of allergy is controversial and some of this controversy may be due to differences in the composition of breast milk between different mothers.Aim: To analyse IgA, cytokine and chemokines levels in human milk and relate the findings to matemal allergy and to development of atopic disease and IgA production in the infants, and furthermore, to assess the effects of breast milk on CBMC cytokine production. To approach these aims, several assays and methods had to be developed.Material and Methods: The levels of total IgA, secretory IgA and ß-lactoglobulin, ovalbumin and Fel d 1 specific IgA antibodies in breast milk and saliva, as well as IL- 4, -5, -6, -8, -10, -13, -16, IFN-γ, TGF-ß, eotaxin, MIP-1α and RANTES in breast milk were analysed by ELISA. Cytokine responses from phytohaemagglutinin, cat dander or ovalbumin stimulated cord blood mononuclear cells were studied in the absence or presence of colostrum.Results: The composition of immunological factors in breast milk varied widely between different mothers. The levels of secretory IgA and ß-lactoglobulin and ovalbumin specific IgA were higher in breast milk from non-allergic than allergic mothers. On the other hand, allergic mothers had higher levels of IL-4, IL-8 and RANTES in their breast milk. There were no relation between the levels of secretory IgA, cytokines and chemokines in breast milk and the development of atopic disease and salivary IgA production in the infants, however. Colostrum inhibited phytohaemagglutinin induced IFN-γ and IL-4 production and cat dander induced IFN-γ production. In contrast, allergen induced IL-5, IL-10 and IL-13 production was enhanced by colostrum. The effects of breast milk on cytokine production were independent of the atopic status of the mothers. The inhibiting effect of colostrum on phytohaemagglutinin induced IFN-γ production correlated with breast milk TGF-β levels, and was partly blocked by the addition of an anti-TGF-ß antibody.Conclusion: There were great individual variations regarding the levels of total and allergen specific IgA, cytokines and chemokines in human milk. Furthermore, breast milk from allergic and non-allergic mothers differed in several aspects. These differences seemed to be of minor importance for the development of atopic disease and IgA production in the breast-fed infant up to two years of age, however. The composition of human milk and the observed effects of breast milk on allergen and mitogen induced cytokine production confirms the anti-inflammatmy properties of human milk, and also suggest possible mechanisms whereby breast-feeding may protect against development of atopic disease. Our results do not support that the effects of breast-feeding are dependent on differences in the immunological composition of the milk, however.
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| 9. |
- Fagerås Böttcher, Malin, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 10. |
- Fagerås Böttcher, Malin, et al.
(författare)
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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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Ingår i: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 70:6, s. 572-577
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Tidskriftsartikel (refereegranskat)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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