Birch Pollen Research Articles

Evaluation of the protocol for rush subcutaneous immunotherapy with birch pollen extract

We previously reported the effectiveness of rush subcutaneous immunotherapy with birch pollen extract (Birch rSCIT) for pollen-food allergy syndrome (PFAS) and the high rate of systemic reactions (SR) during the rapid escalation phase. In this study, we examined whether modifying the dose escalation protocol of Birch rSCIT would reduce SR and maintain therapeutic effects. Birch rSCIT was introduced in 20 patients with PFAS who experienced systemic symptoms upon ingestion of soybeans. Birch rSCIT was implemented using 3 protocols: 2 protocols (nonstep-up group) increased the target dose to more than 1:2 × 102 (w/v) in 0.05 mL, while 1 protocol (step-up group) increased the target dose to 1:2 × 103 (w/v) in 0.3 mL, and then increased to 1:2 × 102 (w/v) in 0.05 mL using the conventional method in the following week. In the nonstep-up group, 4 out of 5 patients (80%), and in the step-up group, 2 out of 15 patients (13.3%) developed SR during rapid escalation. During the rapid escalation phase, the step-up group had significantly fewer SR than the nonstep-up group (P = 0.014). The median ingestible dose of soy milk in the oral food challenge was 3.5 mL before the treatment and increased significantly to 200 mL 1 year after initiating Birch SCIT (P < 0.01). We confirmed that reducing the target antigen dose in Birch rSCIT improved safety and maintained the therapeutic effect for soybean allergy with PFAS.

The SQ tree sublingual immunotherapy tablet is effective and well tolerated in children-A pivotal phase III trial.

Allergic rhinitis and/or conjunctivitis (AR/C) induced by tree pollen is common and negatively impacts quality of life in children and adolescents. This phase III trial investigated the efficacy and safety of the SQ tree SLIT-tablet in a paediatric population (5-17 years) with moderate-to-severe AR/C induced by pollen from birch and trees in the birch homologous group. Nine hundred and fifty-two subjects were randomized (1:1) to daily treatment with SQ tree SLIT-tablet or placebo for up to 52 weeks and had free access to AR/C symptom-relieving medications. The primary endpoint was the average total combined score (TCS); sum of average daily symptom score (DSS) and average daily medication score (DMS) during the birch pollen season (BPS). Key secondary endpoints included average DSS and DMS during BPS and average TCS, DSS and DMS during tree pollen season (TPS). SQ tree SLIT-tablet demonstrated a statistically significant and clinically relevant treatment effect compared with placebo for the TCS during BPS with an absolute treatment difference of 1.29 (95% CI: 0.58, 2.00; p = .0004) and a relative reduction of 21.9% (95% CI: 10.6, 31.9). Results were substantiated by reductions in both DSS and DMS versus placebo during the BPS and in DSS, DMS and TCS during the TPS. Treatment was generally well tolerated. Most treatment-related adverse events were mild or moderate local administration site reactions. This is the first paediatric trial to provide robust evidence of efficacy and safety of the SQ tree SLIT-tablet in tree pollen-induced AR/C in a paediatric population (5-17 years).

Development of a graphene field effect transistor-based immersible biosensor for immunodetection of the birch pollen allergen Bet v 1 in air samples

Pollen traps, the current gold standard to determine pollen load and thereby the allergy season, are not sufficient to determine the allergenic risk. Therefore, the establishment of highly sensitive assays for allergen measurement is of highest interest. Herein, a graphene field-effect transistor (GFET) was constructed on an interdigitated electrodes chip to develop an immersible biosensor, which was used to detect the major birch pollen allergen Bet v 1. Graphene was wet-transferred on interdigitated electrodes that contain a reference electrode used as a liquid gate in the GFET. Using a standard ELISA protocol, two different anti-Bet v 1 antibodies were chosen and immobilized on graphene for the specific capture of the target allergen. The sensitivity of the GFET biosensor was evaluated using a standard Ag/AgCl liquid gate electrode and a reference electrode when the chip was immersed in Bet v 1-containing solutions. The results showed a higher performance and sensitivity for Bet v 1 detection compared to a mediator release method, one of the most sensitive assays for allergen detection. Compared with conventional methods of allergen detection, these immersible biosensors significantly improved the speed and level of detection providing the foundation of a point-of-need platform for in-field application. Furthermore, the proposed technique provides both a new biosensor for allergen detection and a strategy for designing low-cost integrated biosensors.

Allergocomponent diagnostics in the management of comorbid patients

Polyvalent sensitization (simultaneous formation of antibodies to allergens from several sources, for example, to cat allergens, birch pollen, strawberry allergens), which can occur at any age, concerns a significant number of patients with allergic diseases. The diagnostic search for a causal allergen is difficult in patients with polyvalent sensitization and/or cross-reactions to allergens of unrelated groups of allergens. We have carried out work on the detection of polysensitization in patients by the ALEX2 molecular diagnostic method, which detects specific antibodies to 300 allergens (120 allergens and 180 allergenic molecules + total IgE) in one study. The presented clinical examples clearly show the possibility of identifying the spectrum of causal allergens to clarify the diagnosis, which subsequently makes it possible to prescribe the right treatment to prevent the development of complications, which is especially important for comorbid patients

Does living close to allergenic street trees affect lung function in German adults?

IntroductionStudies on greenspace and lung function in adults produced divergent results. Some of the adverse findings could be due to long-term exposure to allergenic tree pollen. We investigated whether having more birch trees or more allergenic trees around home is related to worse lung function and whether these exposures confound the association between greenspace and lung function. MethodsThe analytic sample consisted of 874 adults aged 20–44 years at baseline from the German study centers, Erfurt and Hamburg, of the ECRHS cohort study. Spirometric lung function was measured in 1991/92, 2000/01, and 2011/12. We counted trees based on tree registries and classified them into allergenic and non-allergenic. We assessed exposure to greenspace with the normalized difference vegetation index (NDVI), tree cover density, and total number of trees in a 300 m buffer around home. Linear mixed models were used. ResultsThe forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) were decreased in the presence of more birch trees after adjusting for confounders and co-exposures. For every 10 additional birch trees in a 300 m buffer around home, the average change in FEV1 was −27.6 mL (95% confidence interval (CI): [-58.7, 3.5]). For FVC the average change was −28.2 mL (95% CI: [-62.0, 5.6]). No consistent associations were found for allergenic trees, total trees, tree cover density, or NDVI. Unlike other associations, those of birch trees with FEV1 and FVC were not moderated by allergic sensitization to birch pollen, history of asthma symptoms or nasal allergies including hay fever, ozone, NO2, or age. DiscussionLiving close to birch trees had an adverse long-term association with lung function. That tree registries were limited to street trees prevented us from answering the question of a potential confounding of greenspace effects by allergenic neighborhood trees.

Allergy mapping in children with allergic rhinitis in different subjects of the Russian Federation

Given the climatic and geographical location and differences in the change of seasons in the Russian Federation, there is a marked heterogeneity in the representation of respiratory allergens. Obviously, in the case of double or triple sensitization, the diagnosis of its true picture is a difficult task. In such cases, allergy-component analysis is an extremely necessary stage of allergological examination. Purpose of the study: to assess the sensitization spectrum of AR patients in the age group from 3 to 17 years inclusive, living in different regions of the Russian Federation. Comparative analysis of differences in the sensitization spectrum of AR patients in the Republic of Ingushetia in different age groups. The study involved 47 patients, 36 of them were children under 18 years of age: Moscow n = 9 (Central Federal District), Samara n = 8 (Volga Federal District), Magas n = 19 (North Caucasus Federal District, Republic of Ingushetia). Also, 11 patients aged 18 years and older from Magas city took part in the study. The results obtained by ImmunoCAP ISAC and ALEX2 immune solid-phase allergy test were analyzed. The numerical values of the main respiratory allergens were evaluated, in patients with clinical signs of AR in the period from 01.01.2023 to 27.01.2024. The diagnosis of AR was made according to generally accepted criteria for diagnosis. The main causative factor of AR formation is the major allergen of birch pollen (Bet v1). However, for the Central Federal District, heterogeneity of representation in the group of buciferous trees was noted, which should be taken into account when planning allergen-specific immunotherapy. The spectrum of sensitization of children with AR in the North Caucasian Federal District (Magas) differs significantly from the Central and Volga Federal Districts, where the main major allergen of Amb a 1 ragweed pollen forms the etiological basis of AR formation. When comparing patients with AR of different age groups from Magas city, no differences in the sensitization spectrum were found. The results indicate a high degree of importance of allergy-component diagnostics to improve the effectiveness of allergen-specific immunotherapy.

Silencing of RDR1 and RDR6 genes by a single RNAi enhances lettuce's capacity to express recombinant proteins in transient assays.

Enhanced recombinant protein expression was achieved in Salinas lettuce and commercial lettuce by designing a unique RNAi that knockdown the gene-silencing mechanism in transient assays. Improved yields of recombinant proteins (RP) are necessary for protein-production efficiency and ease of purification. Achieving high yield in non-tobacco plants will enable diverse plants to be used as hosts in transient protein-expression systems. With improved protein yield, lettuce (Lactuca sativa) could take the lead as a plant host for RP production. Therefore, this study aimed to improve RP production in lettuce var. Salinas by designing a single RNA interference (RNAi) construct targeting LsRDR1 and LsRDR6 using the Tsukuba system vector. Two RNAi constructs, RNAi-1 and RNAi-2, targeting common regions of LsRDR1 and LsRDR6 with 75% and 76% similarity, respectively, were employed to evaluate simultaneous gene silencing. Quantitative transcription analysis demonstrated that both RNAi constructs effectively knocked down LsRDR6 and LsRDR1, but not LsRDR2, at both 3 and 5days post-infiltration (dpi), with RNAi-1 exhibited slightly higher efficiency. Based on the protein yield, co-expression of RNAi-1 with enhanced green fluorescent protein (EGFP) increased EGFP expression by approximately 4.9-fold and 3.7-fold at 3dpi and 5dpi, respectively, compared to control. A similar but slightly lower increase (2.4-fold and 2.33-fold) was observed in commercial lettuce at 3and 5 dpi, respectively. To confirm these results, co-infiltration with Bet v 1, a major allergen from birch pollen, resulted in a 2.5-fold increase in expression in Salinas lettuce at 5 dpi. This study marks a significant advancement in enhancing transient protein production in lettuce, elevating its potential as a host for recombinant protein production.

Cross‐protection of AIT‐induced antibodies to related allergens requires a high degree of structural identity

AbstractBackgroundIn contrast to sublingual immunotherapy (SLIT) with recombinant Mal d 1 (rMal d 1‐SLIT), SLIT with rBet v 1 (rBet v 1‐SLIT) induced Mal d 1‐cross‐reactive antibodies without IgE‐blocking activity. To elucidate whether the development of cross‐protective IgG responses depends on the degree of molecular identity of allergens we compared the cross‐reactivity, cross‐blocking activity, and affinity of SLIT‐induced antibodies with allergens of varying amino acid sequence identities to Bet v 1 and Mal d 1, namely Cor a 1.04 (hazelnut), Pru av 1 (cherry), and Dau c 1 (carrot).MethodsAllergen‐specific antibodies were quantified by ELISA. IgE blocking was analyzed by inhibition of allergen‐induced basophil activation and IgE‐facilitated allergen‐presentation to T cells. The affinity of SLIT‐induced antibodies was studied by acidic dissociation ELISA and competition ELISA. Identical surface areas on allergens were predicted using an in‐house designed script based on structural alignments.ResultsrBet v 1‐SLIT‐induced IgG antibodies cross‐reacted with all allergens except Dau c 1. rMal d 1‐SLIT‐induced antibodies predominantly cross‐reacted with Pru av 1 and displayed significantly higher IgE blocking to Pru av 1 than rBet v 1‐SLIT‐induced antibodies. rMal d 1‐SLIT‐induced IgG1 showed higher affinity to Mal d 1 and Pru av 1. Surface analysis revealed 84% identical area on Mal d 1 and Pru av 1. Furthermore, we identified two surface areas potentially containing epitopes present on these allergens and absent on Bet v 1.ConclusionIn summary, our findings suggest that a relatively high threshold of similarity is required to establish effective cross‐blocking antibodies to related allergens. Apparently, the structural identity between Bet v 1 and Mal d 1 is below this threshold. Therefore, this study may explain why immunotherapy with birch pollen allergen often fails to reduce birch pollen‐related apple allergy.

Spatiotemporal modelling of airborne birch and grass pollen concentration across Switzerland: A comparison of statistical, machine learning and ensemble methods

BackgroundStatistical and machine learning models are commonly used to estimate spatial and temporal variability in exposure to environmental stressors, supporting epidemiological studies. We aimed to compare the performances, strengths and limitations of six different algorithms in the retrospective spatiotemporal modeling of daily birch and grass pollen concentrations at a spatial resolution of 1 km across Switzerland. MethodsDaily birch and grass pollen concentrations were available from 14 measurement sites in Switzerland for 2000–2019. To develop the spatiotemporal models, we considered spatiotemporal, spatial and temporal predictors including meteorological factors, land-use, elevation, species distribution and Normalized Difference Vegetation Index (NDVI). We used six statistical and machine learning algorithms: LASSO, Ridge, Elastic net, Random forest, XGBoost and ANNs. We optimized model structures through feature selection and grid search techniques to obtain the best predictive performance. We used train-test split and cross-validation to avoid overfitting and overoptimistic performance indicators. We then combined these six models through multiple linear regression to develop an ensemble hybrid model. ResultsThe 5th-95th percentiles of birch and grass pollen concentrations were 0–151 and 0–105 grains/m3, respectively. The hybrid ensemble model achieved the best RMSE on the test dataset for both birch and grass pollen with 94.4 and 19.7 grains/m3, respectively.Nonlinear models (Random forest, XGBoost and ANNs) achieved lower test RMSE's than linear models (LASSO, Ridge, Elastic net) for both pollen types, with RMSE's ranging from 105.9 to 140.5 grains/m3 for birch and from 20.0 to 25.4 grains/m3 for grass pollen. The Random forest algorithm yielded the best spatial and temporal performance among the six evaluated modelling methods. The ensemble hybrid model outperformed the six linear and nonlinear algorithms. Country-wide pollen concentration, land use, weather, and NDVI were important predictors. ConclusionNonlinear algorithms outperformed linear models and accurately explained complex, nonlinear relationships between environmental factors and measured concentrations.

Optimization of Basophil Activation Test in the Diagnosis and Qualification for Allergen-Specific Immunotherapy in Children with Respiratory Allergy to the House Dust Mite Dermatophagoides pteronyssinus.

The aim of this study was to optimize a basophil activation test in the detection of allergy to the house dust mite Dermatophagoides pteronyssinus in children with allergic respiratory diseases. This study involved 32 cases, 13 girls and 19 boys aged 4-17 years, with perennial asthma or allergic rhinitis caused by D. pteronyssinus. The control group consisted of 13 girls and 19 boys aged 4-17 years with seasonal allergic asthma or rhinitis provoked by Timothy or birch pollen. House dust mite (HDM) allergy was excluded in the controls based on their medical history, skin prick test (SPT) results and sIgE determination. In all patients, a basophil activation test (BAT) was performed with five dilutions of D. pteronyssinus allergen (the dilution series ranged from 22.5 to 0.00225 ng/mL). The results were analyzed by using the receiver operating characteristics (ROC) to determine the optimal allergen concentrations, outcome measures and cut-off points that would differentiate most accurately between HDM-allergic and non-allergic patients. As a "gold standard", criteria for allergen-specific immunotherapy with D. pteronyssinus or respective pollens were applied by an experienced pediatric allergist following the guidelines of the European Academy of Allergy and Clinical Immunology. The highest diagnostic efficiency was yielded by the protocol assuming a cut-off value of 9.76% activated basophils after activation with a single allergen concentration of 2.25 ng/mL (sensitivity 90.6%, specificity 100%). This protocol yielded 3 (4.7%) misclassifications, all false negative, when compared with the "gold standard". There was a strong correlation with the BAT results at 22.5, 2.25 and 0.225 ng/mL (respectively r = 0.90 and r = 0.78, p < 0.001), as well as between the BAT at 2.25 ng/mL and SPT (r = 0.82, p < 0.001) and between the SPT and sIgE levels (r = 0.78, p < 0.001). High cross-reactivity between D. pteronyssinus and D. farinae was confirmed based on the BAT at 22.5 ng/mL (r = 0.82, p < 0.001). In conclusion, the BAT showed very good concordance with the result of a meticulous process of decision-making that combined validated allergy tests (SPT, sIgE) with expert guidelines, specialist knowledge and experience. Facing the risk of the incorrect qualification of patients for costly, long-lasting and potentially risky allergen-specific immunotherapy, the inclusion of a basophil activation test into diagnostic process seems fully justified.

Genetic variability of the major birch pollen allergen Bet v 1 and characterization of B- and T-cell epitopes

The hanging birch pollen collected in the period April – May 2020, 2021 in the territory of six regions of the Republic of Belarus was studied. Recombinant plasmid DNA was obtained. A nucleotide sequence of cloned fragments was determined. The results on the spectrum of isoforms of the Bet v 1 protein were analyzed. The obtained sequences corresponded to one degree or another to 11 genetic variants of the studied allergen. There were 7 isoforms of Bet v 1 defined within one tree. The predominant isoform of the birch pollen allergen Bet v 1 in the territory of the Republic of Belarus was Bet v 1.0101 (Bet v 1a, X15877.1). The identified variants were analyzed for their potential allergenicity by screening amino acids that according to the literature data were identified as affecting IgE-binding. The analysis of amino acid residues included in the IgE-binding conformational epitopes revealed amino acid substitutions exhibiting the multidirectional (high or low) IgE-binding activity in positions 31, 58, 113, 114, 126. The structure of dominant epitopes recognized by the T-cell receptor was studied. It was found that the C-terminal immunodominant T-cell epitope Bet v 1143–157 is highly conserved among various isoforms of the allergen in contrast to the epitope Bet v 178–93 located in the central region. The revealed amino acid substitutions of the studied sites can affect the activation of T-cells, cross-reactivity and significantly increase the variability of the expected IgE-mediated reaction.

Subcutaneous Immunotherapy of Food Allergy.

While there are compelling arguments for developing subcutaneous allergen-specific immunotherapy for alleviation of food allergies, there is a limited number of studies in the public domain. The review seeks to present the approaches taken, to explain the paucity of studies, and to identify new roads for development. A literature search revealed clinical trials of immunotherapy of food allergies to fish and peanut, but studies had limited patient numbers, short treatment courses and follow-up periods. Indications, but no clearcut effects, were seen with both classical allergen extracts and hypo-allergenic preparations. A special case is the influence on cross-reactive food allergies, when subcutaneously administered birch-pollen extracts are used for treatment of birch pollen hayfever and/or asthma. Again indications, but no convincing efficacy has been registered. Newer developments include recombinant hypoallergens and DNA-technologies. Subcutaneous immunotherapy for food allergies has not matured to provide clinically relevant treatment opportunities.

Allergen immunotherapy adverse events in adults with respiratory allergies-data from ADER: An EAACI task force report.

Registries can yield important insights on allergen immunotherapy (AIT) outcomes in daily clinical practice. However, systematic recordings of adverse events (AE) due to AIT in real-life are lacking. The Allergen Immunotherapy Adverse Events Registry (ADER) is a prospective, multicenter registry on real-life AIT safety. Data on adults (>18 years old) with respiratory allergies receiving AIT with mites, pollens, epithelia, and/or molds were retrieved and analyzed from ADER. The frequency, characteristics and risk factors of AE were investigated. The MedDRA terminology was used to record AE. A total of 1545 individuals with a mean age of 33 ± 10 years receiving 1815 AIT courses (n = 1060 sublingual (SLIT); n = 755 subcutaneous (SCIT)) in centers from eight countries were included. Patients had allergic rhinitis (65%) or, asthma only (3.7%) or rhinitis with asthma (31.2%). Grass was the most frequent specific sensitizer (60.7%), followed by mites (45.5%), birch pollen (20.6%), epithelia (16.1%), and molds (8%). There were 296 AE recorded in 115 patients (7.4%). A higher frequency of AE occurred during up-dosing (59%) compared to maintenance. Severe reactions were rare (0.2%), all in the context of SCIT. After 6 weeks of maintenance only one moderate AE was recorded. The most frequently reported symptoms were from the respiratory system and the skin. Having asthma, doing SCIT, AIT with mugwort, cat, or birch were associated with higher risk for AE while the use of allergoids induced lower risk. In real life clinical practice, AIT-associated AE occur in a minority of patients, while severe reactions are rare. The presence of asthma and use of SCIT are risk factors, while the use of modified allergens lowers the risk.

Comparison of two different pollen season definitions based on 10 years of birch and grass pollen data from two distant central European cities: An EAACI Task Force report.

Comparison of two different pollen season definitions based on 10 years of birch and grass pollen data from two distant central European cities: An EAACI Task Force report.

Use of weather types to analyze the simultaneous abundance of ozone, PM2.5 and allergenic tree pollen: focusing on the potential impact on asthma hospitalization in Montreal, Canada

AbstractAir pollution, aeroallergens, and weather conditions can worsen health symptoms such as asthma. While studying the impact of these factors, the use of weather types (WTs) rather than individual meteorological variables (such as temperature, relative humidity, wind, cloudiness, or precipitation) is more appropriate since it is holistic and integrative. Moreover, several studies have shown that the human body responds to WTs, rather than to individual meteorological variables. In this study, the use of Sheridan’s WTs is adopted and compared with a so-called “In-House” WTs. The analysis presented here deals with the links between asthma hospitalization and the synergy among air pollution, birch tree pollen and WTs. Knowing the daily WT in a region can provide valuable information for health planning and management of asthma hospitalization, emergency visits and sub-clinical symptoms in the population. This is because air pollution and birch pollen both occur within only a few specific WTs, such as the TROWAL (trough of warm air aloft) or tropical airmasses. These specific WTs need to be more scrutinized since, in Montreal, these are often linked with higher daily mean hospitalization. The findings of this study emphasize the importance of specific WTs in determining the maximum daily concentrations of ozone, fine particles, Betula pollen concentrations and health effects such as asthma hospitalization. Moreover, the use of data filters in the analysis (for temperature and total count of hospitalization) also reveals new insights in the complex nature of asthma disease and its relationship with environmental factors.

IL-10-modulated dendritic cells from birch pollen- and hazelnut-allergic patients facilitate Treg-mediated allergen-specific and cross-reactive tolerance.

Approximately 70% of individuals allergic to birch pollen (Bet v 1.01 [Bet]) develop a secondary food allergy (e.g., hazelnut: Cor a 1.04 [Cor]), due to allergen cross-reactivity. However, standard immunotherapy for type I allergies often does not improve the food allergy sufficiently. We analyzed the allergen-specific and cross-reactive suppressive capacity of primary human regulatory T cells (Treg) induced by autologous IL-10-modulated dendritic cells (IL-10 DC) invitro and invivo. CD4+ T cells of patients with birch pollen and associated hazelnut allergies were differentiated into Bet-specific or non-specific induced Treg (iTreg). After Bet- or Cor-specific restimulation the phenotype, proliferation, and suppressive capacity of iTreg subsets were analyzed. iTreg function was further investigated in humanized mouse models of airway and intestinal allergy, generated by engraftment of peripheral blood mononuclear cells from allergic donors into immunodeficient animals. After IL-10 DC priming and allergen-specific restimulation (Bet or Cor), non-specific control iTreg remained anergic, whereas Bet-specific iTreg proliferated extensively and exhibited a regulatory phenotype (enhanced expression of CTLA-4, PD-1, TNFR2, IL-10). Accordingly, activated Bet-specific iTreg displayed a high capacity to suppress Bet- and Cor-induced responder Th2 cell responses invitro, indicating induction of both allergen-specific (birch) and cross-reactive tolerance (hazelnut). Invivo, the beneficial effect of Bet-specific iTreg was verified in humanized mouse models of allergic airway and intestinal inflammation, resulting in reduced allergen-induced clinical symptoms, and immune responses. Human IL-10 DC-induced iTreg facilitate allergen-specific and cross-reactive tolerance. Therefore, they are potential candidates for regulatory cell therapy in allergic and autoimmune diseases.

Modulation of Bronchial Epithelial Barrier Integrity by Low Molecular Weight Components from Birch Pollen.

Pollen, in addition to allergens, comprise low molecular weight components (LMC) smaller than 3 kDa. Emerging evidence indicates the relevance of LMC in allergic immune responses. However, the interaction of birch pollen (BP)-derived LMC and epithelial cells has not been extensively studied. We investigated epithelial barrier modifications induced by exposure to BP LMC, using the human bronchial epithelial cell line 16HBE14o-. Epithelial cell monolayers were apically exposed to the major BP allergen Bet v 1, aqueous BP extract or BP-derived LMC. Barrier integrity after the treatments was monitored by measuring transepithelial electrical resistance at regular intervals and by using the xCELLigence Real-Time Cell Analysis system. The polarized release of cytokines 24 h following treatment was measured using a multiplex immunoassay. Epithelial barrier integrity was significantly enhanced upon exposure to BP LMC. Moreover, BP LMC induced the repair of papain-mediated epithelial barrier damage. The apical release of CCL5 and TNF-α was significantly reduced after exposure to BP LMC, while the basolateral release of IL-6 significantly increased. In conclusion, the results of our study demonstrate that BP-derived LMC modify the physical and immunological properties of bronchial epithelial cells and thus regulate airway epithelial barrier responses.

Experience of allergen-specific immunotherapy in the patient with oral and systemic manifestations of birch pollen allergy

Introduction. Allergy to birch pollen is a common allergic disease. The main allergen of birch pollen is Bet v 1. The Bet v 1 protein structure is the similar to proteins of hazel, alder and elm pollen, as well as fruits proteins (apples, apricots, peaches, cherries) and vegetables ones (carrots, celery). Therefore, children with an allergy to the Bet v 1 protein may experience oral allergy syndrome (OAS) and even anaphylaxis when eating these foods. Allergen-specific immunotherapy (ASIT) is the indication for the pollen allergy treatment.Presentation of the clinical case. A 11 years old child was observed with a diagnosis of bronchial asthma, allergic form, moderate persistent clinical course. Pollinosis. Allergic rhinitis. Allergic conjunctivitis. Allergy to birch pollen (Bet v 1). Cross food hypersensitivity: oral syndrome (PR-10 proteins) and anaphylaxis (hazelnuts, peanuts). Systemic manifestations of pollen allergy limit immunotherapy due to the possible development of adverse reactions.The child was prescribed sublingual immunotherapy (SLIT) with the medication “Staloral birch pollen allergen”. Baseline therapy was chosen for the child to achieve control of asthma and rhinitis, a hypoallergenic diet with the exclusion of significant food allergens was prescribed. Asthma and rhinitis exacerbation and OAS was observed during the 1st and 2nd treatment courses. Against the background of baseline therapy, SLIT was continued. The full maintenance dose was achieved during the 3rd SLIT course. Immunotherapy contributed to the reduction of symptoms of rhinitis and asthma, reduction of disease clinical course severity, reduction of baseline medications doses and OAS relief.

Local manifestations of cross food allergy in children with clinical symptoms of respiratory allergy to birch pollen: solutions

Introduction. According to modern data, Oral Allergy Syndrome (OAS) is most often formed by patients sensitized to the birch family: up to 73% of patients allergic to birch experienced OAS. 86% of them experience their oral symptoms year-round, which significantly affects the quality of life of these patients. The effectiveness of AIT in the treatment of respiratory allergy symptoms is beyond doubt, while the effect on the manifestations of cross-food allergies requires additional study.Objective. To study the clinical effectiveness of the formation of oral tolerance to fruits and vegetables under the influence of allergen-specific immunotherapy (ASIT) with the allergen Staloral® “Birch pollen allergen” (Stallergenes Greer, France).Material and methods. The study (prospective open comparative longitudinal) included 184 patients with respiratory allergy to birch pollen aged 5 to 16 years with confirmed sensitization to the major molecule (Bet v 1). Children of the main group (n = 134, 7.0 [5.0; 9.0] years) had OAS. Children from the comparison group (n = 50, 7.0 [6.0; 10.0] years) did not have OAS. A clinical examination, general clinical and allergological examinations were carried out for each child. Component allergy diagnostics was performed using a multiplex panel (ISAC-112, ImmunoCAP) for children with OAS (n = 40) who had multiple manifestations of cross-food allergies. Patients of both groups (n = 184) received a three-year course of AIT with the allergen Staloral® “Birch pollen allergen”.Results. In patients with OAS, it was possible to achieve the formation of oral tolerance (total or partial) to fresh vegetables and fruits in 88.81% (n = 119, p = 0.000). There was a decrease in the intensity and duration of respiratory allergy symptoms during the pollination season, and the need for pharmacotherapy after a three-year course of AIT Staloral® “Birch pollen allergen” in children of both groups.Conclusions: three-year AIT with the allergen Staloral® “Birch pollen allergen” is able to form oral tolerance in children with cross food allergies to PR-10 proteins of vegetables and fruits.

Adoptive Cell Therapy in Mice Sensitized to a Grass Pollen Allergen.

The proportion of patients with type I allergy in the world population has been increasing and with it the number of people suffering from allergic symptoms. Recently we showed that prophylactic cell therapy employing allergen-expressing bone marrow (BM) cells or splenic B cells induced allergen-specific tolerance in naïve mice. Here we investigated if cell therapy can modulate an established secondary allergen-specific immune response in pre-immunized mice. We sensitized mice against the grass pollen allergen Phl p 5 and an unrelated control allergen, Bet v 1, from birch pollen before the transfer of Phl p 5-expressing BM cells. Mice were conditioned with several combinations of low-dose irradiation, costimulation blockade, rapamycin and T cell-depleting anti-thymocyte globulin (ATG). Levels of allergen-specific IgE and IgG1 in serum after cell transfer were measured via ELISA and alterations in cellular responses were measured via an in vitro proliferation assay and transplantation of Phl p 5+ skin grafts. None of the tested treatment protocols impacted Phl p 5-specific antibody levels. Transient low-level chimerism of Phl p 5+ leukocytes as well as a markedly prolonged skin graft survival were observed in mice conditioned with high numbers of Phl p 5+ BMC or no sensitization events between the day of cell therapy and skin grafting. The data presented herein demonstrate that a pre-existing secondary allergen-specific immune response poses a substantial hurdle opposing tolerization through cell therapy and underscore the importance of prophylactic approaches for the prevention of IgE-mediated allergy.