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Biomedical subjects

B Björkstén

Publications and source records attributed to B Björkstén.

At least 19 recordsLinked to original sources

Distinct pattern of commensal gut microbiota in toddlers with eczema.

BACKGROUND: Recent studies have demonstrated differences in the composition of gut microbiota in infants with and without allergic diseases, particularly eczema. METHODS: A case-control study involving 21 toddlers (age 3.0 +/- 0.5 years) with and 28 age-matched toddlers without eczema was conducted. Four groups of aerobic gut microbiota were identified and quantitated in stool samples grown on selective media. Three groups of anaerobes were enumerated by fluorescent in situ hybridization followed by quantitative flow cytometry. We also performed molecular typing of lactic-acid-producing bacteria (LAB) and enterococcal isolates to facilitate detailed analysis at species level by bacterial 16S rDNA sequencing. RESULTS: Toddlers with eczema harbored significantly lower counts of Bifidobacterium [(median 0.14 (25th and 75th percentile: 0.04 and 0.47) vs. 0.71% (0.16, 1.79) of cells acquired, p = 0.003)] and Clostridium [(0.28 (0.09, 0.78) vs. 0.83% (0.35, 1.82) of cells acquired, p = 0.012)] but significantly higher counts of total LAB [7.3 (6.1, 8.5) vs. 5.7 (4.4, 7.3) log CFU/g, p = 0.006] in particular enterococci [6.3 (4.8, 7.4) vs. 5.0 (3.4, 6.4) log CFU/g, p = 0.018]. There was no significant correlation between eczema severity score and bifidobacterial counts. CONCLUSION: The results further confirm previous reports that the gut microecosystem differs between children with and without eczema and extend them beyond infancy.

Bacteroides↗

Cytokine responses to allergens during the first 2 years of life in Estonian and Swedish children.

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 (beta-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.

Allergens↗

Immunoglobulin constant heavy G chain genes as risk factors in childhood allergies.

BACKGROUND: Several candidate genes have been found to be associated with the inflammatory response of IgE-mediated allergy, so also the immunoglobulin constant heavy G chain (IGHG) genes. The IGHG genes are situated close to the IGHE gene on chromosome 14q32, 5'mu, delta, gamma3, gamma1, alpha1, gamma2, gamma4, epsilon, alpha2, 3'. They are inherited in a Mendelian fashion and expressed randomly in allelic exclusion. The alternative and functionally different gamma3, gamma1 and gamma2 gene variants are found in four IGHG haplotypes, coding four B cell variants. OBJECTIVE: The aim of this study was to assess the frequency of different IGHG genes in relation to phenotypes associated with allergy, in a case-control study. METHODS: We identified the constant heavy-chain genes of IgG in 198 allergic and non-allergic children participating in the Phase II of the International Study of Asthma and Allergy in Children. The IGHG genes were assessed by the alternative serum IgG subclass allotypes expressing the alternative alleles of gamma3, gamma1 and gamma2 genes, using ELISA and double immunodiffusion. RESULTS: The IGHG*bfn haplotype (=B1 cells) and IGHG2*n allele dominated (51% vs. 24%, P=0.002) and the IGHG*bf-n haplotype (=B2 cells) was infrequent (16% vs. 52%, P < 0.001) in allergic children with a family history of allergy, clinical manifest allergy and positive skin prick test (SPT). The frequency of IGHG genes was similar in children with maternal and paternal heredity and in children with wheezing, eczema or rhinitis, as well as in children with different positive SPT. The IGHG*bfn haplotype with the IGHG2*n allele was strongly associated with heredity for allergy. The IGHG*bf-n haplotype was inversely related to allergy. Conclusions IgG allotypes, immunochemical and functional variants of IgG molecules from IGHG genes are associated with atopy. The IGHG*bfn haplotype (=B1 cells) with the IGHG2*n allele dominates, associated with an increased risk for atopy. In contrast, the IGHG*bf-n haplotype (=B2 cells) with the IGHG2*-n allele is associated with low risk.

Alleles↗

Prevalence of self-reported food allergy and IgE antibodies to food allergens in Swedish and Estonian schoolchildren.

OBJECTIVE: To compare the prevalence of self-reported food allergy and IgE antibodies to food allergens in wheezing and non-wheezing Estonian and Swedish schoolchildren, in the light of the disparities in the standard of living, food consumption and prevalence of respiratory allergies that still exist between Estonia and the Scandinavian countries. DESIGN AND SETTING: As a part of the ISAAC Phase II study, children from a random sample of schools in Tallinn in Estonia and Linköping and Ostersund in Sweden participated in skin prick tests to inhalant allergens and the parents replied to questionnaires. IgE antibodies against a panel of food allergens (egg white, milk, soy bean, fish, wheat and peanut) were taken from children with questionnaire-reported wheezing and a random sample of nonwheezing children. SUBJECTS: Children aged 10-11 y. RESULTS: The prevalence of self-reported food allergy was similar in Estonia and Sweden and about twice as high in wheezing children than in nonwheezing children. In Estonia, however, 3% of the children with perceived food allergy reported reactions from at least four different foods, as compared to 31% in Sweden. The prevalence of sensitisation to food allergens was similar in wheezing and nonwheezing children in Estonia (8%) while, in Swedish children, IgE antibodies to food allergens were more likely among wheezing children (Linköping 38 vs 11%, crude OR 5.1, 95% CI 2.2-11.6, and Ostersund 24 vs 7%, crude OR 4.1, 95% CI 1.9-8.5). CONCLUSION: Our study suggests that IgE-mediated food reactions were less likely in Estonian schoolchildren. Moreover, the perception of food allergy and thereby the meaning of self-reported food allergy appears to be different in the two countries.

Allergens↗

Atopic sensitization and atopic dermatitis in Estonian and Swedish infants.

BACKGROUND: Early life events seem to have a major impact on the development of tolerance or sensitization. OBJECTIVE: The aim of the study was to compare the prevalence of sensitization and atopic dermatitis (AD) during the first 2 years of life in Estonia and in Sweden. METHODS: Two groups comprising 110 Estonian and 123 Swedish infants were followed from birth up to 2 years of age. Data about symptoms of allergy, infections and use of antibiotics were obtained by questionnaires. Clinical examinations, skin prick tests (SPTs) with food and inhalant allergens, and blood sampling for IgE analyses were carried out at 3, 6, 12 and 24 months. RESULTS: The cumulative incidence of AD and positive SPTs were lower in the Estonian than the Swedish infants (14% vs. 24%; P = 0.06 and 13% vs. 24%; P = 0.03), while circulating IgE antibodies were more common (39% vs. 27%; P = 0.06) and often present without any clinical significance in Estonian children. Estonian infants had respiratory illnesses more often and they had received antibiotics more frequently. Use of antibiotics increased the risk for positive SPT in the Estonian (odds ratio = 1.7, 95% confidence interval = 1.1-2.5), but not in the Swedish infants. This may be explained by the use of broad-spectrum antibiotics in Estonia, while in Sweden mostly penicillin was prescribed. CONCLUSIONS: The prevalence of AD and positive SPTs was lower in the Estonian than the Swedish infants, while circulating IgE antibodies were more common and often present without any clinical significance. These differences cannot simply be explained by infections, or use of broad-spectrum antibiotics in the two countries, although more the natural lifestyle in Estonia may be contributing factor.

Antibodies, Anti-Idiotypic↗

Intestinal microbiota and immunoglobulin E responses in 5-year-old Estonian children.

BACKGROUND: Over the last few decades, several studies from different parts of the world have indicated an increasing prevalence of allergic diseases. This has been related to environmental factors, like changes of microbial pressure. Our previous studies have demonstrated differences in the intestinal microbiota between allergic and non-allergic children. AIM: To test the hypothesis that the intestinal microbiota and IgE response are related, both in allergic and non-allergic 5-year-old Estonian children. METHODS: The study group comprised 19 allergic and 19 non-allergic 5-year-old children, selected from a larger group who had been followed from birth. The diagnosis of allergy was based on clinical examination of the children and on data obtained from the questionnaires. The faecal microbiota were quantified by seeding serial dilutions on nine different media for incubation in different environment. The composition of the gut microbiota was expressed both as absolute counts of the various species and their relative share among the total counts of identified microbiota. RESULTS: Bifidobacteria were less commonly detected in children with allergic diseases than in healthy children and clostridia comprised a higher proportion among their gut microbes. Children with specific IgE antibodies to defined allergens had higher counts of clostridia and the counts of clostridia correlated with the level of serum IgE, but only so in allergic children. In non-allergic children, the serum IgE levels showed a positive correlation with the counts of bacteroides. CONCLUSION: The development of allergic diseases seems to be associated with the composition of the gut microbial ecosystem. High counts of potential pathogens, such as clostridia, are associated with clinical manifestations of allergy and IgE antibody formation.

Bacteroides↗

Cat allergen-induced cytokine secretion and Fel d 1-immunoglobulin G immune complexes in cord blood.

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-gamma, 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-gamma by CBMC was not influenced by maternal atopy, but IFN-gamma 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-gamma seems to be related with the presence of IC in cord blood.

Allergens↗

Atopic disorders among Estonian schoolchildren in relation to tuberculin reactivity and the age at BCG vaccination.

BACKGROUND: Published data about a relationship of atopic diseases to Bacillus Calmette-Guérin (BCG) vaccination and tuberculin responses are inconsistent. Our aim was to determine this association in a country with a low prevalence of allergies. METHODS: A random sample of 10-11-year-old schoolchildren in Tallinn was studied by a parental questionnaire (n = 979) and skin-prick tests (n = 643), according to the International Study of Asthma and Allergies in Childhood. Data about BCG vaccinations and tuberculin tests were obtained from school records (n = 723). RESULTS: The prevalence of allergic symptoms and atopy was similar in children vaccinated during the first month of life and later. Positive tuberculin responses (> or =5 mm) were inversely related to symptoms of asthma [odds ratio (OR) 0.10 (95% confidence interval 0.00-0.68) for exercise-induced wheezing; OR 0.37 (0.12-0.99) for night cough], and eczema [OR 0.53 (0.28-0.98)] but not to atopy. However, among BCG-revaccinated children, atopy tended to be more common in tuberculin responders, and the atopic children were significantly more likely to have a positive tuberculin response after the revaccination than would be predicted by their first test. CONCLUSIONS: We found no protective effect of early BCG vaccination against atopy in school age, although tuberculin responses and allergic symptoms were inversely related.

Age Factors↗

Peripheral blood eosinophils and IL-4 in infancy in relation to the appearance of allergic disease during the first 6 years of life.

Eosinophils in peripheral blood and serum levels of interleukin (IL)-4 were analysed at 3 and 18 months and at 6 years in a prospective study comprising 67 children, of whom the majority had atopic heredity. The children were monitored from birth up to 6 years of age and the findings were related to family history of allergy and development of allergic disease. Twenty-nine children (43%) of the original group of 67 children were diagnosed as allergic at the age of six. Fifteen of 23 children with eosinophilia (>4 x 10(8) eosinophils/l) at 3 months of age were regarded as allergic at 6 years, when compared with 12 out of 38 children with normal eosinophil counts at 3 months (chi2 = 6.7, p < 0.01). Children with detectable IL-4 in serum at 18 months were more often allergic at 6 years, when compared with those children with no detectable IL-4 (chi2 = 8.6, p < 0.01). Furthermore, the allergic children had a mean IL-4 value of 0.35 microg/l (95% CI: 0.10-1.48) at 18 months, when compared with 0.17 microg/l (95% CI: 0.10-0.72, p < 0.001) in the non-allergic children. At 6 years of age, only nine children had detectable levels of IL-4 and five of them were classified as allergic. Eosinophilia at this age was also associated with allergic disease. We conclude that eosinophilia during infancy and increased levels of IL-4 at 18 month of age are associated with allergic disease during the first 6 years of life. This might indicate that the first 2 years of life are particularly important for the development of allergy.

Age Factors↗

Phase II of the International Study of Asthma and Allergies in Childhood (ISAAC II): rationale and methods.

International comparative studies, investigating whether disease incidence or prevalence rates differ between populations and, if so, which factors explain the observed differences, have made important contributions to the understanding of disease aetiology in many areas. In Phase I of the International Study of Asthma and Allergies in Childhood (ISAAC), the prevalence rates of symptoms of asthma, allergic rhinitis and atopic eczema in 13-14-yr-olds, assessed by standardised questionnaires, were found to differ >20-fold between the 155 study centres around the world. Phase II of ISAAC aims to identify determinants of these differences by studying informative populations. A detailed study protocol was developed for use in community-based random samples of children aged 9-11 yrs. The study modules include standardised questionnaires with detailed questions on the occurrence and severity of symptoms of asthma, allergic rhinitis and atopic eczema, their clinical management, and a broad range of previous and current exposure conditions. In addition, standardised protocols were applied for examination of flexural dermatitis, skin-prick testing, bronchial challenge with hypertonic saline, blood sampling for immunoglobulin E analyses and genotyping, and dust sampling for assessment of indoor exposures to allergens and endotoxin. To date, ISAAC II field work had been completed or started in 30 study centres in 22 countries. The majority of centres are in countries that participated in International Study of Asthma and Allergies in Childhood Phase I and reflect almost the full range of the observed variability in Phase I prevalence rates.

Asthma↗

Bronchial hyperresponsiveness in two populations with different prevalences of atopy.

SETTING: Random population samples of young adults from Tartu, Estonia (n = 307) and Uppsala, Sweden (n = 498) in the framework of the European Community Respiratory Health Survey (ECRHS). OBJECTIVE: To compare the prevalence and risk factors for bronchial hyperresponsiveness (BHR) to methacholine in two centres with similar climate and ethnicity but differences in the prevalence of atopy, asthma and respiratory symptoms. DESIGN: General population-based cross-sectional survey. RESULTS: The prevalence of BHR using the cut-off points 1.5, 1.0 and 0.5 mg was 19%, 12% and 8% in Tartu and 11%, 7% and 2%, respectively, in Uppsala. Current smoking was a common risk factor for BHR in both centres. Female sex (odds ratio [OR] 2.9), sensitisation to cat (OR 5.9) and visible mould in the home (OR 2.4) were independent risk factors for BHR in Tartu. In Uppsala, BHR was significantly associated with total IgE levels (OR 2.0) and exposure to environmental tobacco smoke (OR 3.3). CONCLUSION: The high prevalence of BHR can explain the high prevalence of respiratory symptoms in Tartu and indicates that causes other than asthma and atopy can be responsible for the high prevalence of BHR in a population.

Adult↗

Endotoxin levels in Estonian and Swedish house dust and atopy in infancy.

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.

Beds↗

High-dose exposure to cat is associated with clinical tolerance--a modified Th2 immune response?

BACKGROUND: Allergen-specific IgG4 antibodies, it is suggested, may be protecting against allergy development by blocking responses. Levels are proposed as a marker of modified Th2 response. OBJECTIVES: To assess the levels of IgE, IgG1 and IgG4 antibodies to cat in relation to cat exposure, asthma and allergic diseases. METHODS: We studied a population-based sample of 412 schoolchildren of 12-13 years of age. Parents of 402 children completed a questionnaire covering their child's medical history, the keeping of cats and other background data. Skin prick tests (SPTs) to common aeroallergens were performed in 371 of the children. Blood samples for the analyses of IgE, IgG1 and IgG4 antibodies were obtained from 309 of them. RESULTS: All children had an immune response to cat, predominantly of the IgG1 subclass. The levels of cat-specific IgG1 and IgG4, but not IgE, were high in children currently keeping a cat. Children with asthma had increased levels of cat-specific IgE and IgG1, and children with a positive SPT to cat also had increased IgG4. The presence of IgG4 was not associated with asthma or sensitization, unless there was a simultaneous production of IgE. Twenty-five percent of the children had an immune response with only IgG4, and no IgE antibodies to cat. This group of children had the highest frequency of cat-keeping, but a similar prevalence of asthma and allergy as those with neither IgE nor IgG4 antibodies to cat. CONCLUSION: Cat-keeping was associated with a modified Th2 response, producing IgG4 but not IgE antibodies. This immune response was not associated with an increased risk of asthma or allergy. However, the IgG4 antibodies did not directly mediate any protective effect.

Adolescent↗

High body mass index, asthma and allergy in Swedish schoolchildren participating in the International Study of Asthma and Allergies in Childhood: Phase II.

AIM: To assess the relationship between high body mass index (BMI) and asthma and atopic manifestations in 12-y-old children. METHODS: The relationship between high BMI and asthma symptoms was studied in 457 sixth-grade children, with (n = 161) and without (n = 296) current wheeze. High BMI was defined as > or = 75th percentile of gender-specific BMI reference values for Swedish children at 12 y of age; overweight as a subgroup of high BMI was defined as > or = 95th percentile. Children with a BMI < 75th percentile served as controls. Questionnaires were used to assess asthmatic and allergic symptoms, and bronchial hyperresponsiveness was assessed by hypertonic saline provocation tests. RESULTS: Current wheeze was associated with high BMI after adjustment for confounding factors (adjusted OR 1.7, 95% CI 1.0-2.5) and overweight had an even more pronounced effect (adjusted OR 1.9, 95% CI 1.0-3.6). In addition, asthma severity was associated with high BMI, as evaluated by the number of wheezing episodes during the previous 12 mo among the wheezing children (adjusted OR 2.0, 95% CI 1.0-4.0). There was also an association between high BMI and the presence of eczema in wheezing children (adjusted OR 2.2, 95% CI 1.0-4.6). However, high BMI was not significantly associated with hay fever, positive skin prick tests or bronchial hyperresponsiveness. CONCLUSION: The study confirms and extends a previously observed relationship between BMI and the presence of wheezing and asthma.

Adolescent↗

Childhood indicators of susceptibility to subsequent cervical cancer.

Common warts could indicate cervical cancer susceptibility, as both are caused by human papillomavirus (HPV). Eczema was also investigated, as atopic eczema has been negatively associated with warts, but non-atopic eczema may be associated with compromised host defences, as observed in patients with HIV, suggesting increased susceptibility to HPV infection and cervical cancer. 'Cervical cancer' was self-reported during an interview by 87 of 7594 women members of two longitudinal British birth cohorts. The accuracy of the diagnoses is limited by lack of confirmation using medical records. Odds ratios are adjusted for common warts and eczema in childhood; and cigarette smoking, number of cohabiting partners and social class in early adult life. The odds ratios of warts and eczema with cervical cancer are 2.50 (95% confidence interval 1.14-5.47) and 3.27 (1.95-5.49), respectively. The association of eczema with cervical cancer is independent of hay fever as a marker of atopy, suggesting the importance of non-atopic eczema. Both heavier smoking compared with non-smoking and four or more cohabiting partners compared with one/none have odds ratios for cervical cancer of 8.26 (4.25-15.10) and 4.89 (1.39-17.18), respectively. Common warts in childhood may indicate cervical cancer susceptibility; this and the relationship with eczema deserves investigation.

Adolescent↗

Immune responses to birch in young children during their first 7 years of life.

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 Lite and birch-induced mononuclear cell proliferation with 3H-thymidine incorporation. RESULTS: Birch-induced IFN-gamma 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.

Aging↗