| 1. |
- Fagerås Böttcher, Malin, et al.
(author)
-
Slow salivary secretory IgA maturation may relate to low microbial pressure and allergic symptoms in sensitized children
- 2011
-
In: Pediatric Research. - : Nature Publishing Group. - 0031-3998 .- 1530-0447. ; 70:6, s. 572-577
-
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.
|
|
| 2. |
- Lundberg, Anna, et al.
(author)
-
Lower LPS responsiveness in Estonian than Swedish infants associates with less allergy development and high endotoxin exposure
-
Other publication (other academic/artistic)abstract
- Background: Allergic diseases have increased in the last decades, particularly in countries with an affluent lifestyle, possibly due to a reduced or altered microbial exposure during infancy. Objective: The aim of this study was to follow lipopolysaccharide (LPS) induced immune responses prospectively in infants from Estonia and Sweden, i.e. two countries with different frequencies of allergic disease and a different domestic endotoxin exposure. ' Methods: The study included 14 Estonian and 36 Swedish infants who were followed prospectively from birth up to two years of age regarding development of allergy using questionnaires, clinical examinations and skin prick tests. Isolated cord blood mononuclear cells (birth) and peripheral blood mononuclear cells (obtained at 3, 6, 12 and 24 months) were cultured for 24h with LPS in combination with IFN-γ. The secretion of IL-6, CXCL8 (IL-8), IL-10, IL12p70, IL-17, IL-1β, CCL2 (MCP-1), CCL4 (MIP-1β) and TNF was analysed with a Luminex assay. Results: The Swedish, as compared to Estonian children, had higher levels of LPS/IFN-γ induced CCL4 and IL-6 at birth and of IL-1β, IL-12p70, IL-17 and TNF at 3 months as well as IL-6 at 6 months. Also, the levels of CCL2 at 3 and 6 months of age and CCL4 and TNF at 6 months of age were higher in Swedish than Estonian infants in unstimulated cultures. Sensitised Swedish infants had higher levels of LPS/IFN-γ induced IL-10 at 3 and 12 months of age compared to non-sensitised Swedish infants. Conclusion: The enhanced LPS/IFN-γ induced cytokine and chemokine secretion in Swedish, compared to Estonian infants may support a less rapid induction of immune regulation in an affluent society. This could possibly be due to a reduced microbial pressure on Swedish children during early childhood.
|
|
| 3. |
- Norrman, Gunilla, et al.
(author)
-
Significant improvement of eczema with skin care and food elimination in small children.
- 2005
-
In: Acta Paediatr. - : Wiley. - 0803-5253 .- 1651-2227. ; 94:10, s. 1384-8
-
Journal article (peer-reviewed)abstract
- AIM: To evaluate common methods of investigation and treatment in children younger than 2 y of age with eczema, with or without sensitization to food allergens. METHODS: One hundred and twenty-three children younger than 2 y of age with eczema and suspected food allergy were included in this prospective study. The children underwent skin-prick test with cow's milk, fresh hen's egg white and wheat. Specific IgE to milk and egg white was analysed. The eczema extent and severity was estimated with SCORAD before and after treatment. Children with a positive skin-prick test were instructed to exclude that food item from their diet. All children were treated with emollients and topical steroids when needed. RESULTS: Sixty-two of the children were skin-prick positive to at least one of the allergens; 62% had mild, 30% moderate and 8% severe eczema at their first visit. After treatment, 90% had mild, 10% moderate and 0% severe eczema. Forty-six per cent of the children had circulating IgE antibodies to milk or egg white. Ten per cent had specific IgE but negative skin-prick test to the same allergen. This subgroup improved their eczema significantly without elimination diet. CONCLUSION: The conventional treatments for children with eczema, i.e. skin care and food elimination, are effective. The beneficial effect of skin care as the first step should not be neglected, and it may not be necessary to eliminate food allergens to relieve skin symptoms in all food-sensitized children with eczema.
|
|
| 4. |
- Sjögren, Y M, et al.
(author)
-
Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses
- 2009
-
In: Clinical and Experimental Allergy. - : Wiley. - 0954-7894 .- 1365-2222. ; 39:12, s. 1842-1851
-
Journal article (peer-reviewed)abstract
- Introduction Among sensitized infants, those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear.Objective To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous Toll-like receptor (TLR) 2 and TLR4 mRNA expression and lipopolysaccharide (LPS)-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMCs).Methods Fecal samples were collected at 1 week, 1 month and 2 months after birth from 64 Swedish infants, followed prospectively up to 5 years of age. Bacterial DNA was analysed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age 6 and 12 months and at 2 and 5 years and SIgA was measured with ELISA. The PBMCs, collected 12 months after birth, were analysed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMCs were stimulated with LPS, and cytokine/chemokine responses were measured with Luminex.Results The number of Bifidobacterium species in the early fecal samples correlated significantly with the total levels of salivary SIgA at 6 months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMCs. However, PBMCs from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), was inversely correlated to the relative amounts of Bacteroides fragilis in the early fecal samples.Conclusion Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early intense colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
|
|
| 5. |
- Sjögren, Ylva Margareta, 1981-, et al.
(author)
-
Influence of early gut microbiota on the maturation of childhood mucosal and systemic immune responses
-
Other publication (other academic/artistic)abstract
- Introduction: Among sensitized infants those with high, as compared with low levels, of salivary secretory IgA (SIgA) are less likely to develop allergic symptoms. Also, early colonization with certain gut microbiota, e.g. Lactobacilli and Bifidobacterium species, might be associated with less allergy development. Although animal and in vitro studies emphasize the role of the commensal gut microbiota in the development of the immune system, the influence of the gut microbiota on immune development in infants is unclear. Objective: To assess whether early colonization with certain gut microbiota species associates with mucosal and systemic immune responses i.e. salivary SIgA and the spontaneous toll like receptor (TLR) 2 and TLR4 mRNA expression and LPS-induced cytokine/chemokine responses in peripheral blood mononuclear cells (PBMC). Methods: Faecal samples were collected at one week, one month and two months after birth from 64 Swedish infants, followed prospectively to five years of age. Bacterial DNA was analyzed with real-time PCR using primers binding to Clostridium difficile, four species of bifidobacteria, two lactobacilli groups and Bacteroides fragilis. Saliva was collected at age six and twelve months and at two and five years and SIgA was measured with ELISA. The PBMC, collected twelve months after birth, were analyzed for TLR2 and TLR4 mRNA expression with real-time PCR. Further, the PBMC were stimulated with LPS and cytokine/chemokine responses were measured with Luminex. Results: The number of Bifidobacterium species in the early faecal samples correlated significantly with the total salivary SIgA levels at six months. Early colonization with Bifidobacterium species, lactobacilli groups or C. difficile did not influence TLR2 and TLR4 expression in PBMC. However, PBMC from infants colonized early with high amounts of Bacteroides fragilis expressed lower levels of TLR4 mRNA spontaneously. Furthermore, LPS-induced production of inflammatory cytokines and chemokines, e.g. IL-6 and CCL4 (MIP-1β), were inversely correlated to the relative amounts of Bacteroides fragilis in the early faecal samples. Conclusion: Bifidobacterial diversity may enhance the maturation of the mucosal SIgA system and early high colonization with Bacteroides fragilis might down-regulate LPS responsiveness in infancy.
|
|
| 6. |
- Tomicic, Sara, et al.
(author)
-
Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers-relationship to microbial pressure and infant allergy
- 2010
-
In: Pediatric Research. - 0031-3998 .- 1530-0447. ; 68:4, s. 330-334
-
Journal article (peer-reviewed)abstract
- The immune system of the neonate is influenced by maternal immunity during pregnancy and lactation. An altered microbial exposure, possibly underlying the increase of allergic diseases in affluent societies, may affect maternal breast milk immune composition. Secretory IgA (SIgA), IL-4, IL-10, IL-13, IFN-γ, TGF-β1, and TGF-β2 were analyzed with ELISA in colostrum and 1-mo mature milk from mothers from Estonia (n = 39) and Sweden (n = 60), the two geographically adjacent countries with different living conditions and allergy incidence. The IL-10 and IFN-γ levels were higher in colostrum from Estonian than Swedish mothers, whereas the opposite was true for TGF-β2. In mature milk, higher SIgA and IFN-γ levels but lower TGF-β1 and TGF-β2 levels were observed in Estonian than Swedish mothers. Interestingly, in Sweden but not Estonia, the TGF-β1 and TGF-β2 levels correlated inversely with environmental endotoxin concentrations, whereas positive correlations to microbial load were observed for IL-4, IL-10, and IFN-γ. High colostral IL-13 levels were associated with allergic sensitization during infancy in Sweden. In conclusion, Estonian mothers have lower breast milk levels of TGF-β, particularly TGF-β2, but higher levels of SIgA, IL-10, and IFN-γ than Swedish mothers, possibly because of differences in microbial load.
|
|
| 7. |
- Tomičić, Sara, et al.
(author)
-
Dysregulated Th1 and Th2 responses in food-allergic children : Does elimination diet contribute to the dysregulation?
- 2010
-
In: Pediatric Allergy and Immunology. - : Blackwell Publishing Ltd. - 0905-6157 .- 1399-3038. ; 21:4, s. 649-655
-
Journal article (peer-reviewed)abstract
- Infants with eczema and sensitization to foods are recommended skin care and, if food allergy is proven, an elimination diet. Although most of these children tolerate foods before 3 yr of age, some children experience prolonged food allergy. To our knowledge, no prospective study has investigated the cytokine profile in food-sensitized eczematous children with prolonged food intolerance. The aim of the study was to prospectively investigate the development of cytokine production induced by food allergen in food-sensitized eczematous children who, at 41/2 yr of age, were allergic or tolerant to egg or milk. Twenty-one eczematous infants, [age 5 (3-10) months; median and range], sensitized to egg and/or milk were included, put on elimination diet and followed prospectively. At 41/2 yr of age, the children were defined as tolerant or allergic to egg and/or milk based on open or double-blind placebo-controlled food challenges. Peripheral blood mononuclear cells (PBMC) were isolated from the children on inclusion, after 6 wk of elimination diet, and at 3 and 41/2 yr of age. Ovalbumin, beta-lactoglobulin and tetanus toxoid-induced IL-4, -5, -10, -13 and IFN-gamma production from PBMC were analyzed with enzyme-linked immunosorbent assay. The IFN-gamma and IL-5 secretion induced by food allergen at 41/2 yr was higher in cell cultures from children who were allergic to egg or milk than in tolerant children. In food-allergic children, the levels of IFN-gamma and IL-5 were higher at 41/2 yr compared with inclusion levels, but this increase was generally not observed in the tolerant children who consumed milk and egg. In conclusion, immune cells from food-allergic children on an elimination diet respond with up-regulated T helper 1 and T helper 2 cytokine secretion induced by food allergen. We hypothesize that allergen elimination may influence the regulatory mechanisms maintaining balanced immune responses to innocuous food antigens.
|
|
| 8. |
- Tomičić, Sara, 1976-
(author)
-
Environmental and immunological factors associated with allergic disease in children
- 2008
-
Doctoral thesis (other academic/artistic)abstract
- Background: Allergic diseases are characterised by dysregulated immune responses. The first manifestation of the atopic phenotype is often food allergy, with symptoms like eczema. Food allergy in children is generally outgrown before 3 years of age, but a temporary food elimination diet is often advocated. The prevalence of allergic diseases has increased in affluent countries during the last decades, possibly as a consequence of a changed lifestyle leading to decreased microbial load.Aim: To investigate humoral, mucosal and cell-mediated immunity in association to allergy and allergy development in young children and relate this to environmental factors.Subjects: Two cohorts of children were investigated; 1) Children from countries with high (Sweden) and low (Estonia) prevalence of allergy that were followed prospectively from birth to 5 years of age. 2) Infants with eczema and suspected food allergy that were followed prospectively to 4 ½ years of age.Methods: Endotoxin levels were analysed in house dust samples. Antibodies were measured in serum and saliva samples with ELISA. Food allergen induced cytokine responses were analysed in mononuclear cells.Results: The microbial load, delineated as endotoxin levels, was higher in house dust from Estonia than Sweden and was, in Swedish children, inversely associated with sensitisation and clinical symptoms of allergy. The decreased microbial load in Sweden may have an impact on mucosal immune responses as different IgA antibody patterns were observed in Sweden and Estonian children with much lower secretory (S)IgA antibody levels and high proportion of non-SIgA, i.e. IgA antibodies lacking the secretory component, in the Swedish children. Moreover, low levels of SIgA were associated with clinical symptoms in sensitised children.High IgG4 antibody levels to food allergens during infancy were associated with faster tolerance development in food allergic children. Cytokine responses by mononuclear cells after allergen stimulation was upregulated with age in children with prolonged food allergy, but not in children who develop tolerance before 4 ½ years of age, possibly because of the prolonged elimination diet in the former group.Summary: Reduced microbial exposure in affluent countries may affect the mucosal immune responses during infancy, possibly resulting in an increased risk of developing allergic disease. High levels of IgG4 antibodies during infancy are associated with faster achievement of tolerance in food allergic children. Allergen elimination during infancy may result in a dysfunctional cytokine response.
|
|
| 9. |
- Tomičić, Sara, et al.
(author)
-
High levels of IgG4 antibodies to foods during infancy are associated with tolerance to corresponding foods later in life
- 2009
-
In: Pediatric Allergy and Immunology. - : Wiley. - 0905-6157 .- 1399-3038. ; 5:1, s. 35-41
-
Journal article (peer-reviewed)abstract
- Children with eczema and sensitization to foods are recommended skin care and, if food allergy is proven by challenge, an elimination diet. For most children the diet period is transient, but the process behind tolerance development and the influence of decreased allergen exposure is not fully known. The aim of the study was to investigate the effect of elimination diet on serum and salivary antibodies and to identify immunological parameters related to the ability to tolerate foods. Eighty-nine children, below 2 yr of age, with eczema and suspected food allergy were included. Recommended treatment was skin care to all children, and 60 children had a period of elimination diet. At 4½ yr of age, the children were divided into two groups, based on if they had been able to introduce the eliminated foods, or not. Serum and salivary antibodies were analyzed with enzyme-linked immunosorbent assay and UniCAP® before and after a 6-wk treatment period and at 4½ yr of age. Children sensitized to egg and/or milk that could eat and drink the offending foods at 4½ yr of age, had higher levels of Immunoglobulin G4 antibodies to ovalbumin and β-lactoglobulin and also higher IgG4/Immunoglobulin E ratios on inclusion in the study, than those who had to eliminate egg and/or milk from their diet, beyond 4½ yr of age. The highest IgG4/IgE ratios were found in children with circulating IgE antibodies to egg and/or milk but negative skin prick test on inclusion. The 6-wk treatment period did not significantly affect the levels of serum and salivary antibodies. In conclusion, eczematous, food sensitized infants with high levels of IgG4 and high ratios of IgG4/IgE antibodies to food allergens are more likely to consume these foods at 4½ yr than infants with low levels and ratios.
|
|
