Bovine Holo-Beta-Lactoglobulin Cross-Protects Against Pollen Allergies in an Innate Manner in BALB/c Mice: Potential Model for the Farm Effect

The lipocalin beta-lactoglobulin (BLG) is a major protein compound in cow’s milk, and we detected it in cattle stable dust. BLG may be a novel player in the farm protective effect against atopic sensitization and hayfever. In previous studies, we demonstrated that only the ligand-filled holo-form of BLG prevented sensitization to itself. Here, we investigated whether holo-BLG could, in an innate manner, also protect against allergic sensitization to unrelated birch pollen allergens using a murine model. BALB/c mice were nasally pretreated four times in biweekly intervals with holo-BLG containing quercetin–iron complexes as ligands, with empty apo-BLG, or were sham-treated. Subsequently, mice were intraperitoneally sensitized two times with apo-BLG or with the unrelated birch pollen allergen apo-Bet v 1, adjuvanted with aluminum hydroxide. After subsequent systemic challenge with BLG or Bet v 1, body temperature drop was monitored by anaphylaxis imaging. Specific antibodies in serum and cytokines of BLG- and Bet v 1-stimulated splenocytes were analyzed by ELISA. Additionally, human peripheral blood mononuclear cells of pollen allergic subjects were stimulated with apo- versus holo-BLG before assessment by FACS. Prophylactic treatment with the holo-BLG resulted in protection against allergic sensitization and clinical reactivity also to Bet v 1 in an unspecific manner. Pretreatment with holo-BLG resulted in significantly lower BLG-as well as Bet v 1-specific antibodies and impaired antigen-presentation with significantly lower numbers of CD11c+MHCII+ cells expressing CD86. Pretreatment with holo-BLG also reduced the release of Th2-associated cytokines from Splenocytes in BLG-sensitized mice. Similarly, in vitro stimulation of PBMCs from birch pollen allergic subjects with holo-BLG resulted in a relative decrease of CD3+CD4+ and CD4+CRTh2 cells, but not of CD4+CD25+CD127− Treg cells, compared to apo-BLG stimulation. In conclusion, prophylactic treatment with holo-BLG protected against allergy in an antigen-specific and -unspecific manner by decreasing antigen presentation, specific antibody production and abrogating a Th2-response. Holo-BLG therefore promotes immune resilience against pollen allergens in an innate manner and may thereby contribute to the farm protective effect against atopic sensitization.

Comparative prevalence of atopic sensitization in the border areas between Russia and Finland

Current century has been highlighted with rise in allergic pathology, and environment markedly affects it via epigenetic mechanisms. Allergy research in Russia and Finland has been conducted for many years, of larger scale recorded in the latter, still being maintained over time. Atopy prevalence was studied in the border areas in both countries. The level of total, dietary, inhaled IgE level, as well as dietary and inhalation range were examined. The Phadiatop® radio allergen sorbent test was used (UniCAP 1000 v.2; Pharmacia Upjohn, Uppsala, Sweden), with cut-off point: IgE > 110 kUA/l and sIgE > 2.5 kUa/l and 0.35 kUA/l. The study was subdivided into 2 stages conducted during 2003 and 2010/2012 timeframe. Stage 1 was performed with children from Finland (n = 344), Russia (n = 427), aged 7—15 years, whereas stage 2 — 180 subjects (Finland, n = 98, Russia, n = 82). Results. It was found that total IgE level was higher in children from Finland. The inhaled sIgE in 2003 and 2010/2012 was higher among children from Finland, p = 0.019 and p = 0.027, showing temporal elevation. In 2003, dietary sIgE was higher among those from Finland (27.6% and 18.3%), p = 0.142, whereas in 2010/2012 it was decreased by 2- and 3-fold in subjects from Finland and Russia, respectively. In 2003, high atopy rate against dust mites, cats, timothy, birch, and dogs was found in Russia, which was increased at stage 2. Such parameter was most evidently elevated for timothy — by 2-fold, p = 0.176, wormwood — by 2-fold, p = 0.312, equine allergens — by 2-fold, p = 0.563, canine allergens — by 1.5-fold, mite — by 1.5-fold, p = 0.220. In 2003, atopy rate in Finland to canine allergens reached 26.5%, timothy — 24.5%, birch — 20.4%, feline allergens — 20.4%. In 2010, it was noted rise in atopy rate mainly to dust mites — by 2-fold, equine allergens — by 2-fold. In 2003, atopy rate in Russia to egg, milk, and wheat prevailed, whereas in Finland it was mostly found against milk, nuts, wheat, eggs, in both cases declined in dynamics. Interestingly, no sensitization to fish in subjects from Russia and Finland was observed at both stages. Finally, at the stage 2 dietary atopy rate was declined in both countries. Differences in atopic sensitization as well as during 7—9 year follow-up observation were preserved between both subject cohorts from Finland and Russia.

Asthma predictive index as a useful diagnostic tool in preschool children: a cross-sectional study in Korea

Background: It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children.Purpose: This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children.Methods: We performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma.Results: The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed.Conclusion: The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

Efficacy of Brazilian Propolis Supplementation for Japanese Lactating Women for Atopic Sensitization and Nonspecific Symptoms in Their Offspring: A Randomized, Double-Blind, Placebo-Controlled Trial

Propolis is a natural product collected from several plants by honeybees and mixed with beeswax and salivary enzymes. In animal models, propolis suppressed IgE-mediated allergies. However, there is no clinical evidence that propolis prevents human atopic sensitization, to the best of our knowledge. Therefore, a randomized, double-blind, placebo-controlled trial was conducted to assess whether propolis supplementation for lactating women increases or decreases the level of total IgE and antigen-specific IgE in the serum of their offspring (i.e., atopic sensitization) at the time of their first birthday. In addition, whether propolis supplementation improves or worsens nonspecific symptoms (e.g., eczema) in the lactating women and their offspring was also investigated. This trial is registered with UMIN000020794. Eligible pairs of mothers and their offspring (n=80) were randomized to two groups: propolis (n=40) and placebo (n=40). Participants were evaluated every month, and 31 (78%) of the propolis group and 23 (58%) of the placebo group underwent blood tests at the first birthday of the offspring. Total IgE ≥ 10 UA/ml was seen in 26 (84%) infants whose mothers were given propolis, which was not significantly different from the 19 (86%) given placebo (P=0.80). Total IgE as a continuous variable was not significantly different between the propolis and placebo groups (P=0.70). Antigen-specific IgE levels for mites, egg white, cow’s milk, and wheat, as both dichotomous and continuous variables, were not significantly different between the two groups. Both in mothers and their offspring, there were no significant differences in the subjective improvements of nonspecific symptoms between the two groups. Except for one mother who had transient and mild nausea, none of the other mothers or their offspring developed severe adverse events during the follow-up period. In conclusion, compared with placebo, Brazilian propolis supplementation did not influence the risk of atopic sensitization in infants and neither did it improve nor worsen nonspecific symptoms in either mothers or their infants.