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Background: Atopic dermatitis (AD) and food allergy (FA) are common childhood diseases, which may either be interrelated or be the result of skin barrier disruption and gut mucosal dysbiosis. Although some evidence suggests the efficacy of emollients and synbiotics, there is no conclusive evidence on the use of these interventions alone or in combination., Objectives: This study is aimed at identifying the efficacy of emollients and synbiotics in preventing AD and FA in children during the first year of life., Methods: The babies of mothers recruited prenatally received either an emollient, synbiotic, both or neither. The intervention was carried out from birth up to 6 months of age. The age of occurrence of AD and FA were reported in multiple questionnaires at 1, 6, and 9 months and at 1 year of age. AD was diagnosed by a pediatrician at 9 months of age., Results: A -total of 459 babies qualified for the outcome assessment at 1 year of age. Neither the emollient nor the synbiotic showed any effect on reducing the development of AD and FA at 1 year of age., Conclusions: This study did not provide any evidence to show that emollients and synbiotics, alone or in combination are sufficient to prevent the occurrence of AD or FA in children up to 1 year of age., (© 2019 S. Karger AG, Basel.)

Background: Food allergy is a serious health issue affecting roughly 4% of children, with a substantial effect on quality of life. Chicken egg allergy is frequently observed in infants. Therefore, some of them have to exclude hen's eggs from their daily diet to avoid allergenic symptoms. Hen's egg is composed of 2 soluble parts; one is egg white, which has been characterized as the major source of allergenicity, while the other is egg yolk, which is estimated as a miner source. Only 2 allergens from egg yolk, α-livetin (Gal d 5) and YGP42 (Gal d 6), have been described to date., Methods: Sera from 53 patients allergic to hen's eggs and 2 patients allergic to sesame were obtained from the Department of Pediatrics, Chiba University Hospital. The study was performed using SDS-PAGE, IgE immunoblotting, and dot blotting., Results: Seven bands of egg yolk were detected by IgE immunoblotting. Out of these bands, a possible new allergen was further characterized by LC-MS/MS. The 33-kDa band was identified as yolk glycoprotein (YGP40) by LC-MS/MS. A total of 21 of the 53 patients (47%) had YGP40 detected by dot blotting., Conclusions: We identified YGP40 as a new hen's egg yolk allergen and detected 4 sites of YGP40 as linear epitopes., (© 2018 S. Karger AG, Basel.)

Background: Altered regulatory immune responses to microbial stimuli and intestinal colonization of beneficial bacteria early in life may contribute to the development of allergic diseases (e.g., atopic dermatitis [AD]). However, few reports have investigated these factors simultaneously. The purpose of this study was to analyze neonatal immune responses to microbial stimuli as well as intestinal colonization of beneficial bacteria, in relation to the development of AD in a birth cohort., Methods: Pregnant women were recruited, and their infants were followed up until 7 months of age. Levels of interleukin (IL)-10 released from cord-blood mononuclear cells (CBMCs) stimulated with heat-killed gram-positive bacteria (Bifidobacterium bifidum and Lactobacillus rhamnosus GG) and Lactobacillus-derived peptidoglycan were measured. Fecal Bifidobacterium counts at 4 days and 1 month were quantified using real-time polymerase chain reaction. The development of AD was determined by means of a questionnaire at 7 months of age., Results: The levels of released IL-10 were significantly lower in infants with AD (n = 17) than in infants without AD (n = 53) for all stimuli. In infants with fecal Bifidobacterium, the incidence of AD was inversely associated with the release of IL-10 from cord blood mononuclear cells., Conclusion: Our findings suggest that impaired IL-10 production in response to microbial stimuli at birth may be associated with an increased risk of developing infantile AD, even in infants with early colonization of intestinal bifidobacteria., (© 2018 S. Karger AG, Basel.)

Background: A few studies have reported that the quantity of selected cytokines/chemokines in breast milk might be associated with atopic dermatitis (AD). Using the multiplex cytokine assay system, we examined cytokines/chemokines in human milk in order to identify new biomarkers related to AD., Methods: We recruited 49 infants with or without AD who participated in a birth cohort and measured the concentrations of cytokines/chemokines in the colostrum (collected within 4-5 days after birth) and mature milk (collected at 1 month postpartum) received by the infants., Results: There were significant differences in the concentrations of interleukin (IL)-1β and IL-12p40 in the colostrum, and in those of IL-4, eotaxin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interferon (IFN)-α2 and MIP-1α in the mature milk between the milk received by infants who developed AD at the age of 6 months and that received by the control infants. There was weak to moderate correlation between those 6 cytokines/chemokines in mature milk. Atopic history and IgE levels of mothers were not related to cytokine/chemokine concentrations in breast milk. Logistic regression analyses showed that high levels of eotaxin in the mature milk were a risk for the development of AD at 6 months of age., Conclusion: These results suggest that several cytokines/chemokines, especially eotaxin, are potential biomarkers for development of AD in early infancy., (Copyright © 2012 S. Karger AG, Basel.)

Background: Matrix metalloproteinase 12 gene (MMP12) has been shown to be associated with asthma in a Caucasian population. In this study, we investigate whether single-nucleotide polymorphisms (SNPs) of MMP12 are associated with a risk for asthma in a Japanese population., Methods: We tested for an association between SNPs in MMP12 and asthma, including its severity, in a Japanese population (630 pediatric and 417 adult patients with atopic asthma and 336 children and 632 adults as controls). The rs652438 A and G variants (N357S) were generated by site-directed mutagenesis and an assay with artificial peptide substrates was used to compare two types of MMP12 activity. The effect of MMP12 inhibition with MMP12-specific small interfering RNA (siRNA) on chemokine secretion from airway epithelial cells was also tested in vitro., Results: N357S showed a p value <0.05 for childhood and combined (adult plus childhood) asthma in the dominant model [odds ratio (OR) 1.60, 95% confidence interval (CI) 1.00-2.56, p = 0.047; OR 1.40, 95% CI 1.04-1.89, p = 0.028, respectively]. This risk variant is associated with asthma severity in adult patients. In the functional assay, the minor-allele enzyme showed significantly lower activity than the major-allele enzyme. MMP12-specific siRNA suppressed IP-10 secretion from airway epithelial cells upon stimulation with IFN-β., Conclusions: Our results suggest that MMP12 confers susceptibility to asthma and is associated with asthma severity in a Japanese population. MMP12 may be associated with asthma through inappropriate attraction of leukocytes to the inflamed tissue., (Copyright © 2012 S. Karger AG, Basel.)

Background: In developed countries, increasing food allergy prevalence and concern regarding food allergies have been reported. Although the use of complementary and alternative medicine (CAM) for the treatment of allergic diseases has increased in some Western countries, the actual proportion and patterns of CAM use for pediatric food allergies in Japan are still unknown., Methods: Fourteen allergy centers in Japan participated in the study using a questionnaire survey regarding the use of CAM by pediatric patients. A diagnosis of food allergy was made at each hospital by pediatric allergists., Results: Surveys were completed by parents/guardians, and data were collected for a total of 962 pediatric food-allergic patients. Overall, 8.4% of the participants used CAM to treat a food allergy. The major CAM therapies used were herbal teas (22.2%), including several Japanese herbal teas, Chinese herbal medicine (18.5%) and lactic acid bacteria (16%). Among the participants using CAM to treat food allergy, 13.6% thought that the CAM being used was very effective, while 11.1% of participants thought that CAM caused some type of side effect., Conclusions: Our study is the first large-scale national survey regarding the use of CAM in pediatric patients with food allergies in Japan. Unlike in the USA, which has a higher rate of CAM use (17%), approximately 8.4% of food-allergic patients used CAM in Japan. Interestingly, the major types of CAM used in Japan differed from those used in the USA. Cultural differences and food customs may affect the use of CAM., (Copyright © 2012 S. Karger AG, Basel.)

Background: Respiratory syncytial virus (RSV) G protein is involved in Th2-shifted immune response, while F protein has a reverse effect on RSV infection in Th2-prone BALB/c mice. Studies on the human T cell response to F or G protein are few, and the relationship between the immune response to G protein and atopy is not known., Methods: We established CD4+ RSV-specific T cell lines (TCLs) from adult patients with respiratory allergic diseases (allergics) or nonatopic controls (controls), and examined proliferative responses and gamma-interferon (IFN-gamma) and interleukin 4 (IL-4) production in these TCLs upon stimulation with RSV, F or G proteins., Results: 32 and 29 RSV-specific oligoclonal TCLs were established from allergics and controls, respectively. IL-4/IFN-gamma in the culture supernatant of antigen-stimulated TCLs was significantly higher in allergics than in controls (p = 0.042). IL-4/IFN-gamma ratios in the culture supernatants of G-protein-reactive TCLs were significantly higher in allergics than in controls (p = 0.016), while no differences in IL-4/IFN-gamma in culture supernatants of F-protein-reactive TCLs were found between allergics and controls (p = 0.787). IL-4/IFN-gamma in the culture supernatants of G-protein-reactive TCLs was significantly higher than those of F-protein-reactive TCLs in allergics (p = 0.023) but not in controls (p = 0.768)., Conclusion: The results suggest that the T cell response to RSV is influenced by the atopic diathesis as well as by individual RSV antigens, and that G protein may be an important antigen involved in allergy in humans., ((c) 2008 S. Karger AG, Basel.)

Expression of the gut-homing receptor integrin alphaEbeta7, but not cutaneous lymphocyte-associated antigen (CLA), on milk allergen-stimulated cord blood T lymphocytes precedes the development of milk-induced eczema in early infancy. The data indicate the involvement of integrin alphaEbeta7 in the development of infantile allergic eczema and provide a clue to the avoidance of specific allergens and novel therapy targeting homing receptors in food allergy., (Copyright 2001 S. Karger AG, Basel)

Background: In allergic rhinitis, the major symptoms of runny nose, sneezing, and stuffy nose tend to become worse upon waking up in the morning, and yet the mechanisms underlying this phenomenon are poorly understood. We investigated whether the worsening of allergic rhinitis in the morning is associated with changes in the activity of inflammatory cells., Methods: Nasal reactivity to methacholine was assessed twice in 8 children with allergic rhinitis and 8 healthy control subjects at 6.00 a.m. and 3.00 p.m. The amounts of eosinophil cationic protein (ECP), histamine and tryptase in induced nasal secretions and peripheral blood were also measured., Results: Nasal reactivity to methacholine was higher at 6.00 a.m. not only in patients but also in healthy controls. Serum ECP and plasma histamine levels showed no circadian patterns. On the other hand, significantly higher levels of inflammatory activation products were found in nasal secretions at 6.00 a.m., thus showing a direct association with nasal reactivity., Conclusion: These results suggest that the circadian variation in nasal reactivity is associated with changes in the activity of eosinophils and basophilic cells in the nasal mucosa.

In order to investigate T cell recognition of allergens in hen egg allergy, we have established 30 ovalbumin (OVA)-specific T cell lines (TCLs) from peripheral blood mononuclear cells of 6 patients with atopic dermatitis, who are positive for IgE antibodies to OVA and clinically allergic to hen egg, and characterized them for their cytokine production pattern. All TCLs we could study were mainly composed of CD4+ T cells. Most TCLs produced significant amounts of interleukin 4 (IL-4) and IL-5 but no or very little interferon gamma on antigen stimulation, suggesting that these TCLs belong to TH2-type T cells. Restriction elements and epitope specificities were further studied on some TCLs. Antibody blocking of the proliferative responses of the TCLs to OVA indicated that HLA-DR are acting as the dominant restriction elements for these TCLs with minor contribution of HLA-DQ. By use of 187 overlapping synthetic peptides covering the whole sequence of OVA, at least 3 different T cell epitopes were identified.

An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339, which is a major T cell epitope presented by murine I-Ad. The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339-specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL establishment and identification of a T cell epitope possibly related to the allergic reaction to food antigens. An analog peptide of the OVA 323-339 which is known to strongly bind to I-Ad partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy.

We studied the binding activities of IgE, IgG and IgA antibodies in patients with allergy to hen's egg white against two different ovalbumin (OVA) preparations, which were physically or chemically denatured OVA and enzyme-digested OVA fragments. The binding activities of IgE antibodies to these OVA preparations with those of IgG or IgA antibodies were compared. It was found that the binding activities of IgE antibodies to denatured OVA by treatment with dithiothreitol, urea or hydrochloric acid were similar to those of IgG or IgA antibodies. In contrast, the binding activities of IgE antibodies to heat-denatured OVA or by treatment with sodium hydroxide at pH 11.0 were different from those of IgG or IgA antibodies to these denatured OVA. Furthermore, we found that the binding activities of anti-OVA antibodies in sera from patients with allergy to hen's egg white against fragmented OVA were different between IgE antibodies and IgG or IgA antibodies. Thus, it can be concluded that IgE antibodies to OVA in sera from patients with allergy to egg white differ from IgG or IgA antibodies in respect to binding activities against different preparations of denatured or fragmented OVA, probably due to differences in fine specificities of these antibodies against OVA.