| 1. |
- Anthoni, Sari, et al.
(författare)
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Milk protein IgG and IgA : the association with milk-induced gastrointestinal symptoms in adults
- 2009
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Ingår i: World Journal of Gastroenterology. - : Baishideng Publishing Group Inc.. - 1007-9327 .- 2219-2840. ; 15:39, s. 4915-4918
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study the association between serum levels of milk protein IgG and IgA antibodies and milk-related gastrointestinal symptoms in adults. METHODS: Milk protein IgG and IgA antibodies were determined in serum samples of 400 subjects from five outpatient clinics in Southern Finland. Subjects were randomly selected from a total of 1900 adults undergoing laboratory investigations in primary care. All 400 participants had completed a questionnaire on abdominal symptoms and dairy consumption while waiting for the laboratory visit. The questionnaire covered the nature and frequency of gastrointestinal problems, the provoking food items, family history and allergies. Twelve serum samples were disqualified due to insufficient amount of sera. The levels of specific milk protein IgG and IgA were measured by using the ELISA technique. The association of the milk protein-specific antibody level was studied in relation to the milk-related gastrointestinal symptoms and dairy consumption. RESULTS: Subjects drinking milk (n = 265) had higher levels of milk protein IgG in their sera than non-milk drinkers (n = 123, P < 0.001). Subjects with gastrointestinal problems related to milk drinking (n = 119) consumed less milk but had higher milk protein IgG levels than those with no milk-related gastrointestinal symptoms (n = 198, P = 0.02). Among the symptomatic subjects, those reporting dyspeptic symptoms had lower milk protein IgG levels than non-dyspeptics (P < 0.05). However, dyspepsia was not associated with milk drinking (P = 0.5). The association of high milk protein IgG levels with constipation was close to the level of statistical significance. Diarrhea had no association with milk protein IgG level (P = 0.5). With regard to minor symptoms, flatulence and bloating (P = 0.8), were not associated with milk protein IgG level. Milk protein IgA levels did not show any association with milk drinking or abdominal symptoms. The levels of milk protein IgA and IgG declined as the age of the subjects increased (P < 0.004). CONCLUSION: Milk protein IgG but not milk IgA seems to be associated with self-reported milk-induced gastrointestinal symptoms.
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| 2. |
- Cardwell, Chris R, et al.
(författare)
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Breast-Feeding and Childhood-Onset Type 1 Diabetes A pooled analysis of individual participant data from 43 observational studies
- 2012
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 35:11, s. 2215-2225
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE-To investigate if there is a reduced risk of type 1 diabetes in children breastfed or exclusively breastfed by performing a pooled analysis with adjustment for recognized confounders. less thanbrgreater than less thanbrgreater thanRESEARCH DESIGN AND METHODS-Relevant studies were identified from literature searches using MEDLINE, Web of Science, and EMBASE. Authors of relevant studies were asked to provide individual participant data or conduct prespecified analyses. Meta-analysis techniques were used to combine odds ratios (ORs) and investigate heterogeneity between studies. less thanbrgreater than less thanbrgreater thanRESULTS-Data were available from 43 studies including 9,874 patients with type 1 diabetes. Overall, there was a reduction in the risk of diabetes after exclusive breast-feeding for andgt;2 weeks (20 studies; OR = 0.75, 95% CI 0.64-0.88), the association after exclusive breast-feeding for andgt;3 months was weaker (30 studies; OR = 0.87, 95% CI 0.75-1.00), and no association was observed after (nonexclusive) breast-feeding for andgt;2 weeks (28 studies; OR = 0.93, 95% CI 0.81-1.07) or andgt;3 months (29 studies; OR = 0.88, 95% CI 0.78-1.00). These associations were all subject to marked heterogeneity (I-2 = 58, 76, 54, and 68%, respectively). In studies with lower risk of bias, the reduced risk after exclusive breast-feeding for andgt;2 weeks remained (12 studies; OR = 0.86, 95% CI 0.75-0.99), and heterogeneity was reduced (I-2 = 0%). Adjustments for potential confounders altered these estimates very little. less thanbrgreater than less thanbrgreater thanCONCLUSIONS-The pooled analysis suggests weak protective associations between exclusive breast-feeding and type 1 diabetes risk. However, these findings are difficult to interpret because of the marked variation in effect and possible biases (particularly recall bias) inherent in the included studies.
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| 3. |
- Enattah, Nabil Sabri, et al.
(författare)
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Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans
- 2007
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 81:3, s. 615-625
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Tidskriftsartikel (refereegranskat)abstract
- A single-nucleotide variant, C/T-13910, located 14 kb upstream of the lactase gene (LCT), has been shown to be completely correlated with lactase persistence (LP) in northern Europeans. Here, we analyzed the background of the alleles carrying the critical variant in 1,611 DNA samples from 37 populations. Our data show that the T-13910 variant is found on two different, highly divergent haplotype backgrounds in the global populations. The first is the most common LP haplotype (LP H98) present in all populations analyzed, whereas the others (LP H8-H12), which originate from the same ancestral allelic haplotype, are found in geographically restricted populations living west of the Urals and north of the Caucasus. The global distribution pattern of LP T-13910 H98 supports the Caucasian origin of this allele. Age estimates based on different mathematical models show that the common LP T-13910 H98 allele (similar to 5,000-12,000 years old) is relatively older than the other geographically restricted LP alleles (similar to 1,400-3,000 years old). Our data about global allelic haplotypes of the lactose-tolerance variant imply that the T-13910 allele has been independently introduced more than once and that there is a still-ongoing process of convergent evolution of the LP alleles in humans.
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| 4. |
- 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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| 5. |
- Knip, Mikael, et al.
(författare)
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Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes The TRIGR Randomized Clinical Trial
- 2018
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Ingår i: Journal of the American Medical Association (JAMA). - : AMER MEDICAL ASSOC. - 0098-7484 .- 1538-3598. ; 319:1, s. 38-48
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Early exposure to complex dietary proteins may increase the risk of type 1 diabetes in children with genetic disease susceptibility. There are no intact proteins in extensively hydrolyzed formulas. OBJECTIVE To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of type 1 diabetes in young children. DESIGN, SETTING, AND PARTICIPANTS An international double-blind randomized clinical trial of 2159 infants with human leukocyte antigen-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1081 were randomized to be weaned to the extensively hydrolyzed casein formula and 1078 to a conventional formula. The follow-up of the participants ended on February 28, 2017. INTERVENTIONS The participants received either a casein hydrolysate or a conventional adapted cows milk formula supplemented with 20% of the casein hydrolysate. The minimum duration of study formula exposure was 60 days by 6 to 8 months of age. MAIN OUTCOMES AND MEASURES Primary outcome was type 1 diabetes diagnosed according to World Health Organization criteria. Secondary outcomes included age at diabetes diagnosis and safety (adverse events). RESULTS Among 2159 newborn infants (1021 female [47.3%]) who were randomized, 1744 (80.8%) completed the trial. The participants were observed for a median of 11.5 years (quartile [Q] 1-Q3, 10.2-12.8). The absolute risk of type 1 diabetes was 8.4% among those randomized to the casein hydrolysate (n = 91) vs 7.6% among those randomized to the conventional formula (n = 82) (difference, 0.8%[95% CI, -1.6% to 3.2%]). The hazard ratio for type 1 diabetes adjusted for human leukocyte antigen risk group, duration of breastfeeding, duration of study formula consumption, sex, and region while treating study center as a random effect was 1.1 (95% CI, 0.8 to 1.5; P = .46). The median age at diagnosis of type 1 diabetes was similar in the 2 groups (6.0 years [Q1-Q3, 3.1-8.9] vs 5.8 years [Q1-Q3, 2.6-9.1]; difference, 0.2 years [95% CI, -0.9 to 1.2]). Upper respiratory infections were the most common adverse event reported (frequency, 0.48 events/year in the hydrolysate group and 0.50 events/year in the control group). CONCLUSIONS AND RELEVANCE Among infants at risk for type 1 diabetes, weaning to a hydrolyzed formula compared with a conventional formula did not reduce the cumulative incidence of type 1 diabetes after median follow-up for 11.5 years. These findings do not support a need to revise the dietary recommendations for infants at risk for type 1 diabetes.
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| 6. |
- Knip, Mikael, et al.
(författare)
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Hydrolyzed infant formula and early β-cell autoimmunity : a randomized clinical trial.
- 2014
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 311:22, s. 2279-2287
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The disease process leading to clinical type 1 diabetes often starts during the first years of life. Early exposure to complex dietary proteins may increase the risk of β-cell autoimmunity in children at genetic risk for type 1 diabetes. Extensively hydrolyzed formulas do not contain intact proteins.OBJECTIVE: To test the hypothesis that weaning to an extensively hydrolyzed formula decreases the cumulative incidence of diabetes-associated autoantibodies in young children.DESIGN, SETTING, AND PARTICIPANTS: A double-blind randomized clinical trial of 2159 infants with HLA-conferred disease susceptibility and a first-degree relative with type 1 diabetes recruited from May 2002 to January 2007 in 78 study centers in 15 countries; 1078 were randomized to be weaned to the extensively hydrolyzed casein formula and 1081 were randomized to be weaned to a conventional cows' milk-based formula. The participants were observed to April 16, 2013.INTERVENTIONS: The participants received either a casein hydrolysate or a conventional cows' milk formula supplemented with 20% of the casein hydrolysate.MAIN OUTCOMES: AND MEASURES: Primary outcome was positivity for at least 2 diabetes-associated autoantibodies out of 4 analyzed. Autoantibodies to insulin, glutamic acid decarboxylase, and the insulinoma-associated-2 (IA-2) molecule were analyzed using radiobinding assays and islet cell antibodies with immunofluorescence during a median observation period of 7.0 years (mean, 6.3 years).RESULTS: The absolute risk of positivity for 2 or more islet autoantibodies was 13.4% among those randomized to the casein hydrolysate formula (n = 139) vs 11.4% among those randomized to the conventional formula (n = 117). The unadjusted hazard ratio for positivity for 2 or more autoantibodies among those randomized to be weaned to the casein hydrolysate was 1.21 (95% CI, 0.94-1.54), compared with those randomized to the conventional formula, while the hazard ratio adjusted for HLA risk, duration of breastfeeding, vitamin D use, study formula duration and consumption, and region was 1.23 (95% CI, 0.96-1.58). There were no clinically significant differences in the rate of reported adverse events between the 2 groups.CONCLUSIONS AND RELEVANCE: Among infants at risk for type 1 diabetes, the use of a hydrolyzed formula, when compared with a conventional formula, did not reduce the incidence of diabetes-associated autoantibodies after 7 years. These findings do not support a benefit from hydrolyzed formula. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00179777.
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| 7. |
- Pohjavuori, Emma, et al.
(författare)
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Lactobacillus GG effect in increasing IFN-gamma production in infants with cow's milk allergy.
- 2004
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 114, s. 131-136
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Tidskriftsartikel (refereegranskat)abstract
- Background: Probiotic bacteria are potentially beneficial to maturation of the infant's immune system. Objective: To examine the role of probiotic bacteria in treatment of cow's milk allergy (CMA) and IgE-associated dermatitis, we investigated the immunologic effects of Lactobacillus rhamnosus GG (LGG) and a mixture of 4 bacterial species (MIX). Methods: In a randomized, double-blind study design, concomitantly with elimination diet and skin treatment, LGG, MIX, or placebo was given for 4 weeks to infants with suspected CMA. After anti-CD3 (OKT3) and anti-CD28 stimulation of PBMCs, IFN-gamma, IL-4, IL-5, and IL-12 levels were measured in culture supernatants by ELISA. Intracellular IFN-gamma, IL-4, and IL-5 production on CD4 lymphocytes was analyzed with fluorescence-activated cell sorting. Results: Secretion of IFN-gamma by PBMCs before the treatment was significantly lower in infants with CMA (P = .016) and in infants with IgE-associated CMA (P = .003) than in non-CMA infants. Among the infants who received LGG, the level of secreted IFN-gamma increased in those with CMA (P = .006) and in those with IgE-associated dermatitis (P = .017) when compared with the placebo group. Secretion of IL-4 increased significantly in infants with CMA in the MIX (P = .034) but not in the LGG group. Conclusion: Deficiency in IFN-gamma response appears to be related to CMA. LGG raises IFN-gamma production of PBMC in infants with CMA and in infants with IgE-associated dermatitis and may thus provide beneficial T(H)1 immunomodulatory signals. MIX, although containing LGG, appears to modulate the immune responses differently.
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| 8. |
- Savilahti, Erkki, et al.
(författare)
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IgA antibodies, TGF-β1 and -β2, and Soluble CD14 in the colostrum and development of atopy by age 4
- 2005
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Ingår i: Pediatric Research. - : Springer Science and Business Media LLC. - 0031-3998 .- 1530-0447. ; 58:6, s. 1300-1305
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Tidskriftsartikel (refereegranskat)abstract
- Specific defense factors in breast milk together with length of breast-feeding and genetic predisposition may modulate the development of allergy. We studied whether IgA, soluble CD14 (sCD14), or transforming growth factor (TGF)-β in colostrum could affect the development of atopy in children up to age 4. From a cohort of 4676, we selected four groups of children with either long or short exclusive breast-feeding (>3.5 or <0.5 mo), these groups further differed in the presence or absence of atopic heredity. In colostrum from mothers, we measured total IgA, IgA antibodies to cow's milk (CM) and casein, sCD14, and TGF-β1 and -β2. The children were divided into three groups: those with no atopic symptoms or IgE, those with allergic symptoms, and those with both outcomes. Mothers of infants later showing atopic symptoms or, in addition, having IgE sensitization (verified atopy) had a lower concentration of IgA casein antibodies in their colostrum than did mothers of infants with no indication of atopy at age 4. Low concentration of IgA casein antibodies was a significant risk for verified atopy. sCD14 levels were lower in colostrum of mothers with infants developing atopic symptoms and IgE sensitization than of those of infants with no atopy. Specific IgA antibodies to CM antigens and sCD14 in colostrum significantly associated with the appearance of both symptomatic and verified atopy by age 4. Copyright © 2005 International Pediatric Research Foundation, Inc.
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| 9. |
- Sorkio, Susa, et al.
(författare)
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Breastfeeding patterns of mothers with type 1 diabetes: results from an infant feeding trial
- 2010
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Ingår i: DIABETES-METABOLISM RESEARCH AND REVIEWS. - : John Wiley and Sons, Ltd. - 1520-7552 .- 1520-7560. ; 26:3, s. 206-211
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Tidskriftsartikel (refereegranskat)abstract
- Background Both the initiation and maintenance of breastfeeding have been reported to be negatively affected by maternal type 1 diabetes (T1D). The aim of this study was to prospectively examine the breastfeeding patterns among mothers with and without T1D participating in a large international randomized infant feeding trial (TRIGR). Methods Families with a member affected by T1D and with a newborn infant were invited into the study. Those who had HLA-conferred genetic susceptibility for T1D tested at birth with gestation andgt;35 weeks and were healthy were eligible to continue in the trial. Among the 2160 participating children, 1096 were born to women with T1D and 1064 to unaffected women. Information on infant feeding was acquired from the family by frequent prospective dietary interviews. Results Most (andgt;90%) of the infants of mothers with and without T1D were initially breastfed. Breastfeeding rates declined more steeply among mothers with than without T1D being 50 and 72% at 6 months, respectively. Mothers with T1D were younger, less educated and delivered earlier and more often by caesarean section than other mothers (p andlt; 0.01). After adjusting for all these factors associated with the termination of breastfeeding, there was no difference in the duration of breastfeeding among mothers with and without T1D. Conclusions Maternal diabetes status per se was not associated with shorter breastfeeding. The lower duration of breastfeeding in mothers with T1D is largely explained by their more frequent caesarean sections, earlier delivery and lower age and education.
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| 10. |
- Tittanden, M, et al.
(författare)
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Dietary insulin as an immunogen and tolerogen
- 2006
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Ingår i: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 17:7, s. 538-543
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Tidskriftsartikel (refereegranskat)abstract
- We have shown that exposure to bovine insulin (BI) in cow's milk (CM) formula induces an insulin-specific immune response in infants. Here we studied the role of human insulin (HI) in breast milk as a modulator of the immune response to insulin. In a group of 128 children participating in the TRIGR pilot study, maternal breast milk samples were collected 3-7 days and/or 3 months after delivery. After exclusive breast-feeding, the children received either CM formula or casein hydrolysate during the first 6-8 months of life. Insulin concentration in breast milk and immunoglobulin G (IgG) antibodies to BI in plasma samples were measured by EIA. The levels of insulin in breast milk samples were higher in mothers affected by type 1 diabetes than in non-diabetic mothers (p = 0.007 and p < 0.001). The concentration of insulin in breast milk correlated inversely with the plasma levels of IgG antibodies to BI at 6 months of age in children who received CM formula (r = -0.39, p = 0.013), and at 12 months of age in all children (r = -0.25, p = 0.029). The levels of breast milk insulin were higher in the mothers of nine children who developed beta-cell autoimmunity when compared with autoantibody-negative children (p = 0.030), this holds true also when only children of diabetic mothers were included (p = 0.045). BI in CM induces higher levels of IgG to insulin in infants than does HI in breast-fed children. Instead, HI in breast milk seems to be tolerogenic and may downregulate the IgG response to dietary BI. However, our results in infants who developed beta-cell autoimmunity suggest that in this subgroup of children breast milk insulin does not promote tolerance. © 2006 The Authors.
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| 11. |
- Viljanen, Mirva, et al.
(författare)
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Induction of inflammation as a possible mechanism of probiotic effect in atopic ezema-dermatitis syndrome
- 2005
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Ingår i: Journal of Allergy and Clinical Immunology. - : Elsevier BV. - 0091-6749 .- 1097-6825. ; 115:6, s. 1254-1259
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Tidskriftsartikel (refereegranskat)abstract
- Background The immunomodulating mechanisms of Lactobacillus GG (LGG) and other probiotics are poorly understood. Objective We studied in vivo the immunologic effects of probiotics in infants with atopic eczema–dermatitis syndrome (AEDS) and cow's milk allergy (CMA). Methods Two hundred thirty infants with AEDS and suspected CMA received, concomitant with elimination diet, either LGG, a mixture of 4 probiotic strains (MIX), or placebo for 4 weeks. All available paired pretreatment and posttreatment plasma samples (n = 132) were analyzed for concentrations of IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ, soluble intercellular adhesion molecule 1, soluble E-selectin, TGF-β1, TGF-β2, and C-reactive protein. Results In infants with IgE-associated AEDS, treatment with LGG induced higher C-reactive protein levels than in the placebo group (geometric mean, 0.83 μg/mL [95% CI, 0.56-0.81] vs 0.42 μg/mL [95% CI, 0.27-0.65]; P = .021). Concomitantly, IL-6 levels increased after treatment with LGG (P = .023) but not with MIX or placebo. Soluble E-selectin levels were higher after probiotic than after placebo treatment in infants with IgE-mediated CMA (LGG geometric mean, 86.7 ng/mL [95% CI, 75.2-100]; MIX geometric mean, 91.6 ng/mL [95% CI, 74.8-111.9]; and placebo geometric mean, 64.9 ng/mL [95% CI, 53-79.3]; analysis of covariance, P = .035; LGG vs placebo, P = .023; MIX vs placebo, P = .020). Use of MIX induced an increase in plasma IL-10 levels (P = .016). Conclusion Probiotics induced systemically detectable low-grade inflammation, which might explain the clinical effects of probiotics in AEDS and CMA.
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