Real-World Study of Ragweed Sublingual Immunotherapy in Hungary.

BACKGROUND: Ragweed (Ambrosia elatior) has become invasive in Europe, causing significant respiratory issues. Subcutaneous allergen immunotherapy (SCIT) has long been used to manage pollen allergies, but sublingual immunotherapy (SLIT) has gained interest. OBJECTIVE: This study aimed to evaluate the clinical benefits of ragweed SLIT under real-world in a cohort of Hungarian patients allergic to ragweed pollen. METHODS: We retrospectively reviewed the clinical records of 57 patients during the 2015 and 2016 ragweed pollen seasons. Patients were divided into two groups: Group 1 (n = 29), who had not received immunotherapy, and Group 2 (n = 28), who had previously undergone immunotherapy with another sublingual preparation. All patients were treated with Oraltek® ragweed for 4-6 months, initiating 2-4 months before the pollen season and rest of the period was 2 months of the 2016 pollen season. Symptom score (SS), medication score (MS), and combined symptom and medication score (CSMS) were evaluated intra- and intergroup. RESULTS: Pollen counts were consistent between 2015 and 2016. All patients showed significant improvement in SS, MS, and CSMS, with a large effect size (>0.8). Group 2 had significantly lower SS and CSMS in 2015 because of prior immunotherapy. By 2016, both groups exhibited marked improvements, with Group 1 showing a 75% improvement in CSMS. No local or systemic reactions were recorded, indicating a high safety profile. CONCLUSIONS: Ragweed SLIT significantly improved symptoms and reduced use of medication in patients allergic to ragweed pollen. The treatment was effective even in patients with previous immunotherapy, with a high benefit-risk ratio demonstrated by the absence of adverse reactions. These findings support the use of Oraltek SLIT for managing ragweed pollen allergy.

Three-year prognosis after low-dose oral food challenge for children with wheat allergy.

BACKGROUND: Low-dose oral food challenge (LD-OFC) is an approach to avoid complete elimination in high-risk patients with wheat allergy (WA). We examined the 3-year prognosis after LD-OFC among patients who passed and failed LD-OFC. METHODS: Children with immediate-type WA aged ≤6 years with a history of reaction to ≤390 mg of wheat protein underwent their first LD-OFC with 52 mg (baseline LD-OFC). After passing the LD-OFC, children stepped up to 390, 1300, and 5200 mg step-by-step every 3-6 months. After failing LD-OFC, children repeated LD-OFC every 6-12 months. We assessed wheat tolerance defined as consuming 5200 mg without symptoms for 3 years after baseline LD-OFC. RESULTS: The median age of 124 children was 2.4 years, and the wheat- and ω-5-gliadin-specific immunoglobulin E (IgE) levels (kUA/L) were 23.6 and 2.1, respectively. Upon baseline LD-OFC, 57% passed (LD-tolerant), whereas 43% failed (LD-reactive). Within 3 years, 38% of the LD-reactive group passed re-administered LD-OFC, and 70% of all participants avoided complete elimination. The percentage of the participants who became capable of consuming 390 mg (87% vs. 18%), 1300 mg (78% vs. 13%), and acquired tolerance (70% vs. 13%) was significantly higher in the LD-tolerant group than in the LD-reactive group (p < 0.001). Predictors of persistent WA in the LD-tolerant group were older age (adjusted odds ratio, 1.63), ω-5-gliadin-specific IgE level (1.62 per 10-fold increase), and other food allergies (1.94). CONCLUSIONS: LD-tolerant patients frequently acquired wheat tolerance within 3 years. Even if once positive, one-third could pass the re-administered LD-OFC within 3 years.

Effects of rAmb a 1-Loaded PLGA-PEG Nanoparticles in a Murine Model of Allergic Conjunctivitis.

Ambrosia artemisiifolia (Amb a) contains many allergens. Allergic conjunctivitis caused by Ambrosia artemisiifolia and its related allergen-specific immunotherapy (AIT) are seldom studied at present. poly(DL-lactide-co-glycolide)-polyethylene glycol (PLGA-PEG) is a very good nano-carrier, which has been applied in the medical field. In this context, we studied the immunotherapy effect and potential mechanism of recombinant Amb a 1 (rAmb a 1)-loaded PLGA-PEG nanoparticles. A mouse allergic conjunctivitis model was established with Ambrosia artemisiifolia crude extract, and the nanoparticles were used for AIT through direct observation of conjunctival tissue, degranulation of mast cells in conjunctival tissue, serum-specific antibodies, cytokines and other assessment models. The treatment of nanoparticles enhanced the secretion of T-helper 1 (Th1) cytokine Interferon-gama (IFN-γ) and the production of immunoglobulin G (IgG)2a (IgG2a), inhibited the secretion of T-helper 2 (Th2) cytokine Interleukin (IL)-13 and IL-4 and the level of IgE. Especially, degranulation of mast cells and expression of mast cell protease-1 (MCP-1) in conjunctival tissue was reduced significantly. In this study, we proved that the nanoparticles prepared by rAmb a 1 and PLGA-PEG have an immunotherapy effect on allergic conjunctivitis in mice.

Bet v 1 contiguous overlapping peptides anchored to virosomes with TLR4 agonist enhance immunotherapy efficacy in mice.

BACKGROUND: Whereas sublingual allergen immunotherapy (AIT) is routinely performed without any adjuvant or delivery system, there is a strong scientific rationale to better target the allergen(s) to oral dendritic cells known to support regulatory immune responses by using appropriate presentation platforms. OBJECTIVE: To identify a safe presentation platform able to enhance allergen-specific tolerance induction. METHODS: Virosomes with membrane-integrated contiguous overlapping peptides (COPs) of Bet v 1 and TLR4 or TLR2/TLR7 agonists were assessed for induction of Bet v 1-specific IgG1, IgG2a and IgE antibodies, hypersensitivity reactions and body temperature drop following subcutaneous injection in naive CD-1 mice. The most promising candidate, Bet v 1 COPs anchored to virosomes with membrane-incorporated TLR4 agonist (Vir.A-Bet v 1 COPs), was further evaluated by the sublingual route in a therapeutic setting in BALB/c mice with birch pollen-induced allergic asthma. Airway hyperresponsiveness, pro-inflammatory cells in bronchoalveolar lavages and polarization of Th cells in the lungs and spleen were then assessed. RESULTS: Both types of adjuvanted virosomes coupled to Bet v 1 COPs triggered a boosted Th1 immunity. Given a more favourable safety profile, Vir.A-Bet v 1 COPs were further evaluated and shown to able to fully reverse asthma symptoms and lung inflammation in a sublingual therapeutic model of birch pollen allergy. CONCLUSIONS AND CLINICAL RELEVANCE: We report herein for the first time on the capacity of a novel and safe presentation platform, that is virosomes with membrane-integrated TLR4 agonist, to improve dramatically sublingual AIT efficacy in a murine model due to its intrinsic dual properties of targeting and stimulating to further promote anti-allergic immune responses. As such, our study paves the ground for further clinical development of this allergen presentation platform for patients suffering from respiratory allergies.

Peanut oral immunotherapy in a pediatric allergy clinic: Patient factors associated with clinical outcomes.

BACKGROUND: Additional information is needed to inform optimal patient selection, expected outcomes, and treatment end points for clinical peanut oral immunotherapy (OIT). OBJECTIVE: To provide insight into the optimal patient selection, expected outcomes, and treatment end points for clinical peanut oral immunotherapy by analyzing a real-world peanut OIT cohort. METHODS: Records were reviewed for 174 children undergoing peanut OIT at a pediatric allergy clinic. Patient age, peanut skin prick test results, and peanut-specific immunoglobulin E (sIgE) results, with inclusion of additional foods in OIT, were analyzed for correlations with OIT outcomes. RESULTS: To date, 144 patients have achieved maintenance dosing, 50 of whom transitioned to ad lib twice-weekly peanut ingestion. A total of 30 discontinued OIT. In addition, 47 patients who underwent multifood OIT had no significant difference in reactions (FDR-adjusted P = .48) or time-to-reach maintenance (FDR-adjusted P = .48) compared with those on peanut OIT alone. Age at initiation inversely correlated with achievement of maintenance: 92% of patients 0.5 to less than 5 years, 81% of those 5 to less than 11 years, and 70% of those 11 to less than 18 years reached and continued maintenance (P = .01). Baseline peanut-sIgE level positively correlated with number of reactions during updosing (P < .001) and maintenance (P = .005), though it was not significantly different in patients achieving successful maintenance vs those who discontinued OIT (P = .09). Furthermore, 66% of patients experienced greater than or equal to 1 adverse reaction during OIT. Of those on ad lib peanut ingestion, 2 reported mild reactions after lapses in peanut consumption. CONCLUSION: Clinical peanut OIT has similar outcomes to research protocols. OIT can be successful in older children and those with high peanut-sIgE levels, though these factors affect outcomes. Clinical and laboratory criteria can guide successful transition to intermittent ad lib peanut consumption.

Effects of superimposed pressure oscillations on a chronic sensitized airways mouse model.

The hyperconstriction of airway smooth muscle (ASM) is the main driving mechanism during an asthmatic attack. The airway lumen is reduced, resistance to airflow increases, and normal breathing becomes more difficult. The tissue contraction can be temporarily relieved by using bronchodilator drugs, which induce relaxation of the constricted airways. In vitro studies indicate that relaxation of isolated, precontracted ASM is induced by mechanical oscillations in healthy subjects but not in asthmatic subjects. Further, short-term acute asthmatic subjects respond to superimposed pressure oscillations (SIPO) generated in the range of 5-15 Hz with ~50% relaxation of preconstricted sensitized airways. Mechanical oscillations, and specifically SIPO, are not widely characterized in asthmatic models. The objective of this in vivo study is to determine the effects of a range of oscillation patterns similar to our previous acute study differing from normal breathing. Both healthy and sensitized mice were observed, with their responses to SIPO treatments measured during induced bronchoconstriction resulting from acetylcholine (Ach) challenge. SIPO-generated results were compared with data from treatments using the bronchorelaxant isoproterenol (ISO). The study shows that SIPO in the range of 5-20 Hz induces relaxation in chronic sensitized airways, with significant improvements in respiratory parameters at SIPO values near 1.7 cmH2O irrespective of the frequency of generation.

Depletion of microRNA-451 in response to allergen exposure accentuates asthmatic inflammation by regulating Sirtuin2.

The incidence of asthma has increased from 5.5% to near 8% of the population, which is a major health concern. The hallmarks of asthma include eosinophilic airway inflammation that is associated with chronic airway remodeling. Allergic airway inflammation is characterized by a complex interplay of resident and inflammatory cells. MicroRNAs (miRNAs) are small noncoding RNAs that function as posttranscriptional modulators of gene expression. However, the role of miRNAs, specifically miR-451, in the regulation of allergic airway inflammation is unexplored. Our previous findings showed that oxidant stress regulates miR-451 gene expression in macrophages during an inflammatory process. In this paper, we examined the role of miR-451 in regulating macrophage phenotype using an experimental poly-allergenic murine model of allergic airway inflammation. We found that miR-451 contributes to the allergic induction of CCL17 in the lung and plays a key role in proasthmatic macrophage activation. Remarkably, administration of a Sirtuin 2 (Sirt2) inhibitor diminished alternate macrophage activation and markedly abrogated triple-allergen [dust mite, ragweed, Aspergillus fumigatus (DRA)]-induced lung inflammation. These data demonstrate a role for miR-451 in modulating allergic inflammation by influencing allergen-mediated macrophages phenotype.

The dynamic process of dietary soybean ß-conglycinin in digestion, absorption, and metabolism among different intestinal segments in grass carp (Ctenopharyngodon idella).

The present study aimed to investigate the dynamic process of soybean ß-conglycinin in digestion, absorption, and metabolism in the intestine of grass carp (Ctenopharyngodon idella). Fish fed with 80 g ß-conglycinin/kg diet for 7 weeks, the intestinal digestive enzyme was extracted to hydrolyze ß-conglycinin in vitro, the free amino acid and its metabolism product contents in intestinal segments were analyzed. The present study first found that ß-conglycinin cannot be thoroughly digested by fish intestine digestive enzyme and produces new products (about 60- and 55-kDa polypeptides). The indigestible ß-conglycinin further caused the free amino acid imbalance, especially caused free essential amino acid deficiency in the proximal intestine but excess in the distal intestine. Moreover, these results might be partly associated with the effect of ß-conglycinin in amino acid transporters and tight junction-regulated paracellular pathway. Finally, dietary ß-conglycinin increased the content of amino acid catabolism by-product ammonia while decreased the amino acid anabolism product carnosine content in the proximal intestine and distal intestine. Thus, the current study first and systemically explored the dynamic process of ß-conglycinin in digestion, absorption, and metabolism, which further supported our previous study that dietary ß-conglycinin suppressed fish growth and caused intestine injure.

Gender, prick test size and rAra h 2 sIgE level may predict the eliciting dose in patients with peanut allergy: Evidence from the Mirabel survey.

BACKGROUND: Peanut allergy management is based on active avoidance and access to emergency treatment including self-injectable adrenaline. Knowing the dose at which a patient is likely to react is crucial for risk assessment and could significantly improve management by integrating a personalized approach. OBJECTIVE: To develop a threshold dose distribution curve model from routinely collected data. METHODS: The MIRABEL survey is an observational study of 785 patients with peanut allergy/sensitization conducted in France, Belgium and Luxemburg. The current analysis included the 238 participants for whom medical and oral food challenge data were available. Several statistical models (Kaplan-Meier, Cox model, Weibull and Lognormal with predictive factors, basic Weibull and Lognormal) were compared to select the best model and predictive factor combination associated with the threshold doses. Inferences were made with a Bayesian approach. RESULTS: Patients were mainly children (mean age: 9 years [IQR: 6-11]; 87% < 16 years) and males (62%). Median Ara h2 s IgE was of 8kUA/L [IQR: 1-55] and median skin prick test size of 10 mm [IQR: 7-13]. OFC was positive in 204 patients (86%). The median threshold dose was of 67 mg of peanut protein [IQR: 16-244]. The dose at which 1% of the patients are likely to react with objective symptoms was 0.26 [0.03; 2.24] mg of peanut protein. Gender, size of the skin prick test (SPT) and Ara h 2 specific IgE level had a significant impact on the threshold dose distribution curve. The Cox model was the most effective to predict threshold doses with this combination of factors. Girls react to lower doses than boys with a beta coefficient associated to the risk and a 95% credible interval of 0.44 [0.04; 0.77]. The higher the size of the SPT and the Ara h 2 specific IgE level are, the higher the risk of reacting to a small amount of peanut, with beta coefficients associated to the risk and 95% credible intervals of 0.05 [0.02; 0.08] and 0.01 [0.01; 0.02], respectively. CONCLUSION AND CLINICAL RELEVANCE: According to the model, routinely collected data could be used to estimate the threshold dose. The consequences could be the identification of high-risk patients who are susceptible to react to small amounts of peanut and a personalized management of peanut allergy integrating the risk of allergic reaction. Limitations of this study are that assessors of OFC outcome were aware of SPT and Arah2 results, and a further validation study is required to confirm the predictive value of these parameters.

Comparison of Six Different Allergen Extracts for Subcutaneous Specific Immunotherapy in Children: An Open-Labelled, Prospective, Controlled Observational Trial.

BACKGROUND: Numerous products are available for subcutaneous (SCIT) and sublingual allergen-specific immunotherapy, but there are no information about the direct comparability regarding efficacy, safety, and tolerability of the different extracts. AIMS: The aim of this open-labelled, prospective, controlled observational trial was to test the feasibility of a comparison of different products for SCIT in children. METHODS: Pediatrician practices recruited patients with a confirmed diagnosis of a seasonal allergic rhinoconjunctivitis (AR) with or without asthma and an allergic sensitization against grass pollen allergen. Every patient was offered SCIT with one out of six allergen extracts: ALK SQ Depot, ALK Avanz, Allergovit, Depigoid, Purethal, Pollinex Quattro. Scores for symptoms and medications were calculated and the difference between treatment years and baseline were recorded. RESULTS: In total, 284 were recruited and 255 children (89.8%; mean age 10.4, SD 3.54 years; 65% males) participated in this trial. Overall, 49,649 patient days were recorded in the electronic database (mean 183.2 days/patient). There was no significant difference in the AR and asthma symptom score or the medication score between the six different SCIT preparations. Similarly, no differences were observed in terms of safety and tolerability. CONCLUSION: The comparison of different SCIT products using an online tool is feasible. Based on our preliminary data, all extracts indicated efficacy; however, larger groups would be necessary to demonstrate superiority or non-inferiority of one specific SCIT product.

Epicutaneous Exposure to Peanut Oil Induces Systemic and Pulmonary Allergic Reaction in Mice.

BACKGROUND: The prevalence of peanut allergy (PA) is constantly on the rise. Atopic dermatitis (AD) is a major risk factor for developing food allergy. Some bath oils and skin creams used for treating AD contain peanut oil, and it has been suggested that exposure to peanut allergens through a disrupted skin barrier is a potential cause of PA. Our aim was to investigate whether application of peanut oil to irritated skin causes a systemic or respiratory allergic response to peanuts in an animal model. METHODS: BALB/c mice underwent epicutaneous sensitization with either peanut oil (PM, n = 9) or phosphate buffered solution (controls, n = 9) daily for 5 consecutive days. Ten days after the last exposure the mice were challenged with intranasal peanut protein for 5 consecutive days. Bronchial alveolar lavage fluid was collected for cellular studies and measurement of cytokine levels. Sera were collected for immunoglobulin E (IgE) measurement. RESULTS: Epicutaneous peanut oil sensitization increased leukocyte and eosinophil counts and interleukin-13 levels (p = 0.003, p = 0.0006 and p = 0.03, respectively), in addition to increasing total serum IgE (p = 0.03). CONCLUSIONS: The results suggest that topical application of peanut oil may play a role in the etiology of PA.

Estimated risk reduction to packaged food reactions by epicutaneous immunotherapy (EPIT) for peanut allergy.

BACKGROUND: Peanut allergy is a generally persistent, sometimes life-threatening food allergy. With no treatments demonstrating the ability to cure a food allergy, the focus of drugs in development has been on providing a level of protection against accidental exposure reactions. However, no study has estimated the relative risk reduction of a food-allergic population receiving a specific immunotherapeutic treatment for their allergies. OBJECTIVE: To estimate the relative risk reduction when consuming peanut-contaminated packaged food products in a double-blind, placebo-controlled Phase 3 study population of children treated with epicutaneous immunotherapy (EPIT) for 12 months with either a patch containing 250 µg peanut protein (250-µg patch) or a placebo patch. METHODS: The probability of an allergic reaction due to the unintended presence of peanut protein in packaged food products was modeled per study group and food category combination using Monte Carlo simulations. Risks per eating occasion of a contaminated packaged food product and the number of individuals per study population predicted to react on a yearly basis were investigated. RESULTS: The population treated with the 250-µg patch demonstrated a significantly increased dose-response distribution after 12 months of treatment, which resulted in a relative risk reduction of 73.2% to 78.4% when consuming peanut-contaminated packaged food products. In contrast, no statistically significant change was observed for the placebo group at the 12-month point. CONCLUSION: Our study estimates a substantial relative risk reduction for allergic reactions among peanut-allergic children after 12 months of EPIT with the 250-µg patch, supporting the potential real-world clinical relevance of this investigational immunotherapy and its possible role as a future therapy for peanut-allergic children. ClinicalTrials.gov Identifier: NCT02636699.

Effects of glycinin and ß-conglycinin on growth performance and intestinal health in juvenile Chinese mitten crabs (Eriocheir sinensis).

This study investigates the effects of two soybean antigens (glycinin and ß-conglycinin) as an antinutritional substance in the diet on the growth, digestive ability, intestinal health and microbiota of juvenile Chinese mitten crabs (Eriocheir sinensis). The isonitrogenous and isolipidic diets contained two soybean antigens at two levels each (70 and 140 g/kg ß-conglycinin, 80 and 160 g/kg glycinin) and a control diet without ß-conglycinin or glycinin supplementation, and were used respectively to feed juvenile E. sinensis for seven weeks. Dietary inclusion of either glycinin or ß-conglycinin significantly reduced crab survival and weight gain. The crabs fed diets containing soybean antigens had higher malondialdehyde concentrations and lower catalase activities in the intestine than those in the control. The activities of trypsin and amylase in the intestine were suppressed by dietary ß-conglycinin and glycinin. Dietary glycinin or ß-conglycinin impaired the immunity and morphological structure of intestine, especially the peritrophic membrane. The mRNA expression of constitutive and inducible immune responsive genes (lipopolysaccharide-induced TNF-α factor and interleukin-2 enhancer-binding factor 2) increased while the mRNA expression of the main genes related to the structural integrity peritrophic membrane (peritrophin-like gene and peritrophic 2) significantly decreased in the groups with soybean antigen addition. Soybean antigen could also change the intestinal microbial community. The abundance of pathogenic bacteria (Ochrobactrum, Burkholderia and Pseudomonas) increased significantly in both soybean antigen groups. Although pathogenic bacteria Vibrio were up-regulated in the glycinin group, the abundance of Dysgonomonas that degraded lignocellulose and ameliorated the gut environment decreased in the glycinin group. This study indicates that existence of soybean antigens (glycinin or ß-conglycinin) could induce gut inflammation, reshape the community of gut microbiota, and cause digestive dysfunction, ultimately leading to impaired growth in crabs.

Pru p 3 sublingual immunotherapy ultra-rush protocol is safe and clinically effective.

Summary: Introduction. Sublingual immunotherapy (SLIT) with Pru p 3 can prevent severe allergic reactions to LTP-containing foods, but the standard initiation protocol is time-consuming. Objectives. Establish the safety of a novel ultra-rush initiation protocol for SLIT with Pru p 3. Methods. Prospective study comparing the side effects of the standard vs novel ultra-rush initiation protocols of SLIT with Pru p 3 in patients with anaphylaxis to LTP. Results. Fifteen patients were included (standard initiation, 5; ultra-rush initiation, 10), 80% females. All patients had oropharyngeal pruritus during initiation, 80% with spontaneous recovery, but no other gastro-intestinal, respiratory, cutaneous or systemic side effects occurred in any patient of both groups. Conclusion. The novel ultra-rush protocol halved the build-up time without increasing side effects.

Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen-related apple allergy.

BACKGROUND: Birch pollen-related apple allergy is among the most prevalent food allergies in adolescent/adult subjects and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy. OBJECTIVE: We sought to compare the safety and efficacy of sublingual immunotherapy (SLIT) with 2 formulations containing either rMal d 1 or rBet v 1 on birch pollen-related apple allergy. METHODS: Sixty participants with birch pollen-related apple allergy were randomized to daily sublingual application of placebo (n = 20) or 25 µg of rMal d 1 (n = 20) or rBet v 1 (n = 20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG4 antibodies were performed before and after treatment. RESULTS: Both formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared with the placebo and rBet v 1-treated groups, SLIT with rMal d 1 reduced rMal d 1-induced oral symptoms (P = .001 and P = .038) accompanied by longitudinally reduced rMal d 1-specific cutaneous reactions (P = .022) and enhanced IgG4/IgE ratios (P = .012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1-specific IgG4/IgE ratios. Participants receiving placebo showed no allergen-specific changes. CONCLUSION: Sublingual treatment with a recombinant food allergen was safe and clinically effective, as determined by using standardized challenges. We present a promising approach for the effective treatment of birch pollen-related apple allergy.

A randomized, double-blind, placebo-controlled, dose-finding trial with Lolium perenne peptide immunotherapy.

BACKGROUND: A novel subcutaneous allergen immunotherapy formulation (gpASIT+™) containing Lolium perenne peptides (LPP) and having a short up-dosing phase has been developed to treat grass pollen-induced seasonal allergic rhinoconjunctivitis. We investigated peptide immunotherapy containing the hydrolysate from perennial ryegrass allergens for the optimum dose in terms of clinical efficacy, immunogenicity and safety. METHODS: This prospective, double-blind, placebo-controlled, phase IIb, parallel, four-arm, dose-finding study randomized 198 grass pollen-allergic adults to receive placebo or cumulative doses of 70, 170 or 370 µg LPP. All patients received weekly subcutaneous injections, with the active treatment groups reaching assigned doses within 2, 3 and 4 weeks, respectively. Efficacy was assessed by comparing conjunctival provocation test (CPT) reactions at baseline, after 4 weeks and after completion. Grass pollen-specific immunoglobulins were analysed before and after treatment. RESULTS: Conjunctival provocation test (CPT) response thresholds improved from baseline to V7 by at least one concentration step in 51.2% (170 µg; P = .023), 46.3% (370 µg), and 38.6% (70 µg) of patients receiving LPP vs 25.6% of patients receiving placebo (modified per-protocol set). Also, 39% of patients in the 170-µg group became nonreactive to CPT vs 18% in the placebo group. Facilitated allergen-binding assays revealed a highly significant (P < .001) dose-dependent reduction in IgE allergen binding across all treatment groups (70 µg: 17.1%; 170 µg: 18.8%; 370 µg: 26.4%). Specific IgG4 levels increased to 1.6-fold (70 µg), 3.1-fold (170 µg) and 3.9-fold (370 µg) (mPP). CONCLUSION: Three-week immunotherapy with 170 µg LPP reduced CPT reactivity significantly and increased protective specific antibodies.

Intranasal administration of allergen increases specific IgE whereas intranasal omalizumab does not increase serum IgE levels-A pilot study.

BACKGROUND: Administration of the therapeutic anti-IgE antibody omalizumab to patients induces strong increases in IgE antibody levels. OBJECTIVE: To investigate the effect of intranasal administration of major birch pollen allergen Bet v 1, omalizumab or placebo on the levels of total and allergen-specific IgE in patients with birch pollen allergy. METHODS: Based on the fact that intranasal allergen application induces rises of systemic allergen-specific IgE, we performed a double-blind placebo-controlled pilot trial in which birch pollen allergic subjects were challenged intranasally with omalizumab, placebo or birch pollen allergen Bet v 1. Total and allergen-specific IgE, IgG and basophil sensitivity were measured before and 8 weeks after challenge. For control purposes, total, allergen-specific IgE levels and omalizumab-IgE complexes as well as specific IgG levels were studied in subjects treated subcutaneously with either omalizumab or placebo. Effects of omalizumab on IgE production by IL-4/anti-CD40-treated PBMCs from allergic patients were studied in vitro. RESULTS: Intranasal challenge with Bet v 1 induced increases in Bet v 1-specific IgE levels by a median of 59.2%, and this change differed significantly from the other treatment groups (P = .016). No relevant change in allergen-specific and total IgE levels was observed in subjects challenged with omalizumab. Addition of omalizumab did not enhance IL-4/anti-CD40-induced IgE production in vitro. Significant rises in total IgE (mean IgE before: 131.83 kU/L to mean IgE after: 505.23 kU/L) and the presence of IgE-omalizumab complexes were observed after subcutaneous administration of omalizumab. CONCLUSION: Intranasal administration of allergen induced rises of allergen-specific IgE levels, whereas intranasal administration of omalizumab did not enhance systemic total or allergen-specific IgE levels.

The Relationship of Pollen Dispersal with Allergy Symptoms and Immunotherapy: Allergen Immunotherapy Improves Symptoms in the Late Period of Japanese Cedar Pollen Dispersal.

BACKGROUND: The severity of symptoms of pollen-induced allergic rhinitis is affected by the amount of scattered pollen. However, the relationships between the pollen dispersal pattern, symptom severity, and treatment efficacy are not clear. METHODS: Between 2007 and 2012, we performed 4 randomized, placebo-controlled studies of sublingual immunotherapy (SLIT) on patients with Japanese cedar-induced allergic rhinitis who lived in or around Chiba, Japan. The participants were asked to avoid using rescue medicines during the cedar pollen season as much as possible and to record their nasal symptoms in allergy diaries. The amount of pollen dispersed daily was quantified using the Durham method, and the season was divided into early and late periods based on the pollen count. RESULTS: A total of 721 patients were enrolled in the 4 studies during the 6-year study period. In the placebo group (n = 349), a correlation was observed between the amount of pollen dispersed and the severity of symptoms in the early but not late period of pollen dispersal. Treatment with SLIT (n = 372) significantly improved symptom severity in the late but not early period. CONCLUSION: For patients with Japanese cedar pollen-induced allergic rhinitis, the fluctuation of daily pollen dispersal had a minimal effect on the severity of symptoms during the late period. SLIT was remarkably effective in alleviating symptoms during this period but not in the early period.

Soya protein ß-conglycinin ameliorates fatty liver and obesity in diet-induced obese mice through the down-regulation of PPARγ.

Diets high in fat can result in obesity and non-alcoholic fatty liver disease (NAFLD). The improvement of obesity and NAFLD is an important issue. ß-Conglycinin, one of the soya proteins, is known to prevent hyperlipidaemia, obesity and NAFLD. Therefore, we aimed to investigate the effects of ß-conglycinin on the improvement of obesity and NAFLD in high-fat (HF) diet-induced obese (DIO) mice and clarify the mechanism underlying these effects in liver and white adipose tissue (WAT). DIO male ddY mice were divided into six groups: HF, medium-fat (MF) and low-fat (LF) groups fed casein, and HF, MF and LF groups in all of which the casein was replaced by ß-conglycinin. A period of 5 weeks later, the ß-conglycinin-supplemented group resulted in lower body weight, relative weight of subcutaneous WAT, and hepatic TAG content (P=0·001). Furthermore, ß-conglycinin suppressed the hepatic expression of Pparγ2 in the HF dietary group, sterol regulatory element-binding protein-1c and the target genes. The expressions of inflammation-related genes were significantly low in the epididymal and subcutaneous WAT from the mice fed ß-conglycinin compared with those fed casein in the HF dietary group. Moreover, the expressions of Pparγ1 and Pparγ2 mRNA were suppressed in subcutaneous WAT in the HF dietary group but not in epididymal WAT. The concentrations of insulin and leptin were low in the serum of the mice fed ß-conglycinin. In conclusion, ß-conglycinin effectively improved obesity and NAFLD in DIO mice, and it appears to be a promising dietary protein for the amelioration of NAFLD and obesity.

Evaluation of serum IgE in peach-allergic patients with systemic reaction by using recombinant Pru p 7 (gibberellin-regulated protein).

BACKGROUND: Lipid transfer protein (LTP) is a major fruit allergen. It has, however, recently been revealed that the systemic reaction in peach-allergic patients is related not only to LTP (Pru p 3) but also to gibberellin-regulated protein (Pru p 7). We investigated recombinant Pru p 7 (rPru p 7) for its potential use in worldwide standardization for the diagnosis of peach allergy. METHODS: Natural Pru p 7 (nPru p 7) was purified from peach crude extract using a monoclonal antibody affinity column. Complementary DNA for Pru p 7 was cloned and expressed in Escherichia coli and Pichia pastoris. Serum immunoglobulin (Ig) E in peach-allergic patients was examined by enzyme-linked immunosorbent assay (ELISA) using nPru p 7 and rPru p 7 (E. coli product: erPru p 7 and P. pastoris product: prPru p 7). RESULTS: Peach-allergic patients (n=27) were diagnosed and categorized into oral reaction (n=10) or systemic reaction (n=17). The nPru p 7 positivity based on serum IgE levels was 52% in the systemic-reaction group and 0% in the oral-reaction group (P<0.05). In the systemic-reaction group, there was no significant difference in reactivity between nPru p 7 and prPru p 7, but the reactivity of erPru p 7 was significantly lower than those of nPru p 7 and prPru p 7 (P<0.05). CONCLUSIONS: We found that prPru p 7 exhibited reactivity in ELISA comparable to that of nPru p 7 for the diagnosis of peach allergy with systemic reaction.