Birch Pollen Allergen Research Articles

Isolation of nanobodies with potential to reduce patients' IgE binding to Bet v 1

Recent studies showed that a single injection of human monoclonal allergen-specific IgG antibodies significantly reduced allergic symptoms in birch pollen-allergic patients. Since the production of full monoclonal antibodies in sufficient amounts is laborious and expensive, we sought to investigate if smaller recombinant allergen-specific antibody fragments, that is, nanobodies, have similar protective potential. For this purpose, nanobodies specific for Bet v 1, the major birch pollen allergen, were generated to evaluate their efficacy to inhibit IgE-mediated responses. A cDNA-VHH library was constructed from a camel immunized with Bet v 1 and screened for Bet v 1 binders encoding sequences by phage display. Selected nanobodies were expressed, purified, and analyzed in regards of epitope-specificity and affinity to Bet v 1. Furthermore, cross-reactivity to Bet v 1-homologues from alder, hazel and apple, and their usefulness to inhibit IgE binding and allergen-induced basophil activation were investigated. We isolated three nanobodies that recognize Bet v 1 with high affinity and cross-react with Aln g 1 (alder) and Cor a 1 (hazel). Their epitopes were mapped to the alpha-helix at the C-terminus of Bet v 1. All nanobodies inhibited allergic patients' polyclonal IgE binding to Bet v 1, Aln g 1, and Cor a 1 and partially suppressed Bet v 1-induced basophil activation. We identified high-affinity Bet v 1-specific nanobodies that recognize an important IgE epitope and reduce allergen-induced basophil activation revealing the first proof that allergen-specific nanobodies are useful tools for future treatment of pollen allergy.

Chemical and Biological Characteristics of Oxytropis pseudoglandulosa Plant of Mongolian Origin.

Oxytropis pseudoglandulosa is used in Mongolian traditional medicine due to its numerous reported health-promoting effects. To date, there are very few scientific reports that describe this species. In this article, its volatile oil composition, lipid extract composition, total phenolic and flavonoid content, antibacterial and allergenic properties are elucidated for the first time. Hexadecanoic acid, fokienol and tricosane were determined as the most notable components of the volatile oil, at 13.13, 11.46 and 5.55%, respectively. Methyl benzoate was shown to be the most abundant component of lipid extract at 40.69, followed by (E)-prop-2-enoic acid, 3-phenyl- and benzenepropanoic acid, at 18.55 and 9.97%. With a TPC of 6.620 mg GAE g−1 and TFC of 10.316 mg QE g−1, the plant extract of O. pseudoglandulosa indicated good antioxidant activity measured by IC50 at 18.761 µg mL−1. Of the 12 tested microorganisms, B. subtilis and S. cerevisiae were the shown to be most susceptible to the plant extract, with MIC at 2.081 and 0.260% (v/v), respectively. Bet v 1—a major birch pollen allergen found in plant-based foods—was determined to be at 192.02 ng g−1 with ELISA. Such a wide spectrum of biological activity indicated by O. pseudoglandulosa lends credence for its application in food industry. Its exerted antioxidant and antimicrobial effects could improve preservation of low-processed food dedicated for consumers afflicted with allergies. Hexadecanoic acid supplemented in foods with dietary plant extracts could add to the potential anti-inflammatory impact. The analysis of lipid makeup suggests O. pseudoglandulosa extract could also be considered as natural pesticide in organic farming.

The Fusion Protein rFlaA:Betv1 Modulates DC Responses by a p38-MAPK and COX2-Dependent Secretion of PGE2 from Epithelial Cells.

Developing new adjuvants/vaccines and better understanding their mode-of-action is an important task. To specifically improve birch pollen allergy treatment, we designed a fusion protein consisting of major birch pollen allergen Betv1 conjugated to the TLR5-ligand flagellin (rFlaA:Betv1). This study investigates the immune-modulatory effects of rFlaA:Betv1 on airway epithelial cells. LA-4 mouse lung epithelial cells were stimulated with rFlaA:Betv1 in the presence/absence of various inhibitors with cytokine- and chemokine secretion quantified by ELISA and activation of intracellular signaling cascades demonstrated by Western blot (WB). Either LA-4 cells or LA-4-derived supernatants were co-cultured with BALB/c bone marrow-derived myeloid dendritic cells (mDCs). Compared to equimolar amounts of flagellin and Betv1 provided as a mixture, rFlaA:Betv1 induced higher secretion of IL-6 and the chemokines CCL2 and CCL20 from LA-4 cells and a pronounced MAPK- and NFκB-activation. Mechanistically, rFlaA:Betv1 was taken up more strongly and the induced cytokine production was inhibited by NFκB-inhibitors, while ERK- and p38-MAPK-inhibitors only suppressed IL-6 and CCL2 secretion. In co-cultures of LA-4 cells with mDCs, rFlaA:Betv1-stimulated LA-4 cells p38-MAPK- and COX2-dependently secreted PGE2, which modulated DC responses by suppressing pro-inflammatory IL-12 and TNF-α secretion. Taken together, these results contribute to our understanding of the mechanisms underlying the strong immune-modulatory effects of flagellin-containing fusion proteins.

Prophylactic and Therapeutic Effects of Oral Immunotherapy on Birch Pollen-Induced Allergic Conjunctivitis in Mice with a Rice-Based Edible Vaccine Expressing a Hypoallergenic Birch Pollen Allergen.

We investigated the prophylactic and therapeutic effects of the oral administration of transgenic rice seeds expressing a hypoallergenic Bet v 1 derivative of allergic birch pollen conjunctivitis in mice. Transgenic rice seed depositing a chimeric molecule called TPC7 (tree pollen chimera 7) created by DNA shuffling of Bet v 1 family sequences from birch, alder and hazel in protein bodies of endosperm was generated. BALB/c mice were sensitized to birch pollen in alum and challenged with pollen in eyedrops. They were fed TPC7 transgenic or non-transgenic (control) rice seeds for 14 d before sensitization (prophylactic protocol) or 17 d after sensitization (therapeutic protocol). The clinical score and number of conjunctival eosinophils were significantly lower in TPC7-fed mice than in the control mice based on both the prophylactic and therapeutic protocols. Serum concentration of allergen-specific IgE did not differ between TPC7-fed and control groups in either protocol. Prophylactic administration of TPC7 downregulated the production of IL-4 and IFN-γ, whereas therapeutic administration of TPC7 upregulated the production of IFN-γ by allergen-stimulated splenocytes. Prophylactic or therapeutic oral administration of transgenic rice expressing TPC7 suppressed birch pollen-induced allergic conjunctivitis in mice. Feeding transgenic rice is a potentially effective approach as an allergen-specific immunotherapy for allergic conjunctivitis.

Preventive Administration of Non-Allergenic Bet v 1 Peptides Reduces Allergic Sensitization to Major Birch Pollen Allergen, Bet v 1.

IgE-mediated allergy to birch pollen affects more than 100 million patients world-wide. Bet v 1, a 17 kDa protein is the major allergen in birch pollen responsible for allergic rhinoconjunctivitis and asthma in birch pollen allergic patients. Allergen-specific immunotherapy (AIT) based on therapeutic administration of Bet v 1-containing vaccines is an effective treatment for birch pollen allergy but no allergen-specific forms of prevention are available. We developed a mouse model for IgE sensitization to Bet v 1 based on subcutaneous injection of aluminum-hydroxide adsorbed recombinant Bet v 1 and performed a detailed characterization of the specificities of the IgE, IgG and CD4+ T cell responses in sensitized mice using seven synthetic peptides of 31-42 amino acids length which comprised the Bet v 1 sequence and the epitopes recognized by human CD4+ T cells. We then demonstrate that preventive systemic administration of a mix of synthetic non-allergenic Bet v 1 peptides to 3-4 week old mice significantly reduced allergic immune responses, including IgE, IgG, IgE-mediated basophil activation, CD4+ T cell and IL-4 responses to the complete Bet v 1 allergen but not to the unrelated major grass pollen allergen Phl p 5, without inducing Bet v 1-specific allergic sensitization or adaptive immunity. Our results thus demonstrate that early preventive administration of non-allergenic synthetic T cell epitope-containing allergen peptides could be a safe strategy for the prevention of allergen-specific IgE sensitization.

The Flagellin:Allergen Fusion Protein rFlaA:Betv1 Induces a MyD88- and MAPK-Dependent Activation of Glucose Metabolism in Macrophages.

TLR5 ligand flagellin-containing fusion proteins are potential vaccine candidates for many diseases. A recombinant fusion protein of flagellin A and the major birch pollen allergen Bet v 1 (rFlaA:Betv1) modulates immune responses in vitro and in vivo. We studied the effects of rFlaA:Betv1 on bone marrow-derived macrophages (BMDMs). BMDMs differentiated from BALB/c, C57BL/6, TLR5−/−, or MyD88−/− mice were pre-treated with inhibitors, stimulated with rFlaA:Betv1 or respective controls, and analyzed for activation, cytokine secretion, metabolic state, RNA transcriptome, and modulation of allergen-specific Th2 responses. Stimulation of BMDMs with rFlaA:Betv1 resulted in MyD88-dependent production of IL-1β, IL-6, TNF-α, IL-10, CD69 upregulation, and a pronounced shift towards glycolysis paralleled by activation of MAPK, NFκB, and mTOR signaling. Inhibition of either mTOR (rapamycin) or SAP/JNK-MAPK signaling (SP600125) resulted in dose-dependent metabolic suppression. In BMDM and T cell co-cultures, rFlaA:Betv1 stimulation suppressed rBet v 1-induced IL-5 and IL-13 secretion while inducing IFN-γ production. mRNA-Seq analyses showed HIF-1a, JAK, STAT, phagosome, NLR, NFκB, TNF, TLR, and chemokine signaling to participate in the interplay of cell activation, glycolysis, and immune response. rFlaA:Betv1 strongly activated BMDMs, resulting in MyD88−, MAPK−, and mTOR-dependent enhancement of glucose metabolism. Our results suggest macrophages are important target cells to consider during restauration of allergen tolerance during AIT.

Recombinant Bet v 1-BanLec chimera modulates functional characteristics of peritoneal murine macrophages by promoting IL-10 secretion

Allergen-specific immunotherapy (AIT) is a desensitizing treatment for allergic diseases that corrects the underlined pathological immune response to innocuous protein antigens, called allergens. Recombinant allergens employed in the AIT allowed the production of well-defined formulations that possessed consistent quality but were often less efficient than natural allergen extracts. Combining recombinant allergens with an adjuvant or immunomodulatory agent could improve AIT efficacy. This study aimed to perform structural and functional characterization of newly designed recombinant chimera composed of the Bet v 1, the major birch pollen allergen, and Banana Lectin (BanLec), TLR2, and CD14 binding protein, for the application in AIT. rBet v 1-BanLec chimera was designed in silico and expressed as a soluble fraction in Escherichia coli. Purified rBet v 1-BanLec (33.4 kDa) retained BanLec-associated biological activity of carbohydrate-binding and preserved IgE reactive epitopes of Bet v 1. The chimera revealed secondary structures with predominant β sheets. The immunomodulatory capacity of rBet v 1-BanLec tested on macrophages showed changes in myeloperoxidase activity, reduced NO production, and significant alterations in the production of cytokines when compared to both rBanLec and rBet v 1. Comparing to rBet v 1, rBet v 1-BanLec was demonstrated to be more efficient promoter of IL-10 production as well as weaker inducer of NO production and secretion of pro-inflammatory cytokines TNFα, and IL-6. The ability of rBet v 1-BanLec to promote IL-10 in together with the preserved 3D structure of Bet v 1 part implies that the construct might exert a beneficial effect in the allergen-specific immunotherapy.

Structure and Zeatin Binding of the Peach Allergen Pru p 1.

Peach (Prunus persica) is among the fruits most frequently reported to cause food allergies. Allergic reactions commonly result from previous sensitization to the birch pollen allergen Bet v 1, followed by immunological cross-reactivity of IgE antibodies to structurally related proteins in peach. In this study, we present the three-dimensional NMR solution structure of the cross-reactive peach allergen Pru p 1 (isoform Pru p 1.0101). This 17.5 kDa protein adopts the canonical Bet v 1 fold, composed of a seven-stranded β-sheet and three α-helices enclosing an internal cavity. In Pru p 1, the inner surface of the cavity contains an array of hydroxyl-bearing amino acids surrounded by a hydrophobic patch, constituting a docking site for amphiphilic molecules. NMR-guided docking of the cytokinin molecule zeatin to the internal cavity of Pru p 1 provides a structure-based rationale for the effect that zeatin binding has on the protein’s RNase activity.

NMR resonance assignments of the PR-10 allergens Act c 8 and Act d 8 from golden and green kiwifruit

Kiwifruits have become one of the most common food sources triggering allergic reactions. In patients suffering from birch pollen related food allergy, reactions result from initial sensitization to the birch (Betula verrucosa) pollen allergen Bet v 1, followed by immunological cross-reactivity to structurally homologous proteins in kiwifruit. Clinical symptoms range from scratching and itching of the oral cavity to more severe immunological reactions such as rhino conjunctivitis. In this work we assigned backbone and side chain 1H, 13C and 15N chemical shifts of the 17 kDa PR-10 allergens Act c 8.0101 and Act d 8.0101 from golden (Actinidia chinesis) and green (Actinidia deliciosa) kiwifruit by solution NMR spectroscopy. The chemical shift data confirm the characteristic Bet v 1 fold for both proteins, consisting of a seven-stranded antiparallel β-sheet interrupted by two short α-helices, along with a long C-terminal α-helix. Our data provide the basis for determining the three-dimensional solution structures of these proteins and characterizing their immunological cross-reactivity on a structural basis.

The Influence of Air Pollution on the Development of Allergic Inflammation in the Airways in Krakow’s Atopic and Non-Atopic Residents

Until now, the simultaneous influence of air pollution assessed by measuring the objective marker of exposition (1-hydroxypirene, 1-OHP) and atopy on the development of allergic airway diseases has not been studied. The aim of this study was to determine the pathomechanism of the allergic response to PM2.5 in atopic and non-atopic patients. We investigated the changes in peripheral blood basophil activity of patients after stimulation with the birch pollen allergen alone, the allergen combined with PM2.5 (BP), PM2.5 alone, a concentration of 1-OHP in urine, and a distance of residence from the main road in 30 persons. Activation by dust alone was positive for all concentrations in 83% of atopic and 75% of non-atopic assays. In the group of people with atopy, the simultaneous activation of BP gave a higher percentage of active basophils compared to the sum of activation with dust and birch pollen alone (B + P) for all concentrations. The difference between BP and B + P was 117.5 (p = 0.02) at a PM concentration of 100 μg. Such a relationship was not observed in the control group. The correlation coefficient between the distance of residence from major roads and urinary 1-OHP was 0.62. A Pearson correlation analysis of quantitative variables was performed, and positive correlation results were obtained in the atopy group between BP and 1-OH-P. Exposure to birch pollen and PM2.5 has a synergistic effect in sensitized individuals. The higher the exposure to pollutants, the higher the synergistic basophil response to the allergen and PM in atopic patients.

Sensitization profile to sawtooth oak component allergens and their clinical implications

ObjectiveThe component allergens from sawtooth oak, which is a main cause of tree pollinosis in Korea, have not been extensively characterized except Que ac 1. This study was undertaken to characterize the allergenic components from sawtooth oak pollen and investigate the diagnostic values of each component allergen.MethodsTranscriptomic analysis was performed to identify the birch pollen allergen homologues from sawtooth oak pollen. Recombinant Que ac 1, 2, 3, 6, 7, and 8 were produced in an E. coli expression system. IgE reactivity to each allergen was examined by ImmunoCAP and ELISA using the sera of 50 Korean tree pollinosis patients.ResultsSix birch pollen allergen homologues were identified using transcriptome analysis, as follows: Que ac 1 (54.8% identity to Bet v 1), Que ac 2 (79.7% to Bet v 2), Que ac 3 (24.9% to Bet v 3), 6 (71.3% to Bet v 6), Que ac 7 (80.9% to Bet v 7), and Que ac 8 (78.9% to Bet v 8). Que ac 1 sIgE was the most frequently recognized (84.0%), followed by Que ac 2 (12.0%), Que ac 3 (6.0%), and three other allergens (2.0% each). Que ac 1 was a dominant allergen affecting 83.7% of patients suffering from allergic rhinoconjunctivitis, and 92.9% of pollen food allergy syndrome patients.ConclusionFive novel IgE reactive components of sawtooth oak were characterized using transcriptome analysis. Que ac 1 is the single most important component allergen of sawtooth oak pollen.

РАСПРОСТРАНЕННОСТЬ АЛЛЕРГИЧЕСКОГО РИНИТА И БРОНХИАЛЬНОЙ АСТМЫ СРЕДИ ГОРОДСКИХ ДЕТЕЙ ДОШКОЛЬНОГО ВОЗРАСТА: РЕЗУЛЬТАТЫ ОДНОМОМЕНТНОГО ИССЛЕДОВАНИЯ

The aim of the trial was to study the prevalence and clinical and allergic characteristics of allergic rhinitis (AR) and bronchial asthma (BA) in urban preschool children. Materials and methods of research: a one-minute study was carried out on an urban sample of 3–6 year olds (n=3205), consisting of 2 stages – screening and clinical. The study of the prevalence of AR and BA symptoms at the screening stage was carried out by questioning parents using the ISAAC questionnaire. At the clinical stage, the diagnosis of AR and BA was verified based on the diagnostic criteria of the ARIA (2008 revision) and GINA (updated 2017) documents. At the clinical stage, skin prick testing with extracts of inhalation and food allergens from Allergopharma Joachim Ganzer KG (Germany) was carried out. Results: the prevalence of AR and BA among urban children 3–6 years of age was 10,6 and 5,7%, respectively. 80 (52,0%) children with AR and 42 (32,8%) children with BA have not previously been diagnosed in practical healthcare institutions. 107 (69,5%) children with AR and 76 (59,4%) children with BA had a mild severity of the disease, 4 (2,6%) children with AR and 2 (1,6%) children with BA had major severity. 80 (62,5%) of children with BA are diagnosed with a controlled course of the disease and 48 (37,5%) have a partially controlled/uncontrolled course of the disease. Most often, in children with AR and BA, sensitization to the D. pteronyssinus mite was recorded – 95 (61,%) and 68 (53,1%), birch pollen – 63 (40,9%) and 42 (32,8%) and cat allergens – 30 (19,5%) and 20 (15,6%), respectively. Conclusion: the prevalence of AR and BA among preschool children was 10,6 and 5,7%, respectively. More than half of children with AR and 1/3 of children with BA do not have a diagnosis established in practical health care institutions. Most often, in 3–6 years old children with AR and BA, sensitization to the D. pteronyssinus mite, birch pollen and cat allergens is recorded.

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.

Pre- and Neonatal Imprinting on Immunological Homeostasis and Epithelial Barrier Integrity by Escherichia coli Nissle 1917 Prevents Allergic Poly-Sensitization in Mice.

A steady rise in the number of poly-sensitized patients has increased the demand for effective prophylactic strategies against multi-sensitivities. Probiotic bacteria have been successfully used in clinics and experimental models to prevent allergic mono-sensitization. In the present study, we have investigated whether probiotic bacteria could prevent poly-sensitization by imprinting on the immune system early in life. We used two recombinant variants of probiotic Escherichia coli Nissle 1917 (EcN): i) EcN expressing birch and grass pollen, poly-allergen chimera construct (EcN-Chim), and ii) an “empty” EcN without allergen expression (EcN-Ctrl). Conventional mice (CV) were treated with either EcN-Chim or EcN-Ctrl in the last week of the gestation and lactation period. Gnotobiotic mice received one oral dose of either EcN-Chim or EcN-Ctrl before mating. The offspring from both models underwent systemic allergic poly-sensitization and intranasal challenge with recombinant birch and grass pollen allergens (rBet v 1, rPhl p 1, and rPhl p 5). In the CV setting, the colonization of offspring via treatment of mothers reduced allergic airway inflammation (AAI) in offspring compared to poly-sensitized controls. Similarly, in a gnotobiotic model, AAI was reduced in EcN-Chim and EcN-Ctrl mono-colonized offspring. However, allergy prevention was more pronounced in the EcN-Ctrl mono-colonized offspring as compared to EcN-Chim. Mono-colonization with EcN-Ctrl was associated with a shift toward mixed Th1/Treg immune responses, increased expression of TLR2 and TLR4 in the lung, and maintained levels of zonulin-1 in lung epithelial cells as compared to GF poly-sensitized and EcN-Chim mono-colonized mice. This study is the first one to establish the model of allergic poly-sensitization in gnotobiotic mice. Using two different settings, gnotobiotic and conventional mice, we demonstrated that an early life intervention with the EcN without expressing an allergen is a powerful strategy to prevent poly-sensitization later in life.

IgE-binding and mast cell–activating capacity of the homologue of the major birch pollen allergen and profilin from Cannabis sativa

Cannabis is a flowering plant in the family of Cannabaceae, and the most widespread species is Cannabis sativa. In the past decade, cannabis allergy (CA) has been recognized as an increasing health issue and its prevalence is likely underestimated because of cannabis's illegal status in many countries and the absence of reliable diagnostics. The clinical presentation of CA is very heterogeneous, varying from mild rhinoconjunctivitis, urticaria, and angioedema to life-threatening anaphylaxis. Not seldom, CA is associated with a broad cross-reactivity syndrome involving fruits, vegetables, nuts, cereals, and latex.

Treatment Effect of the Tree Pollen SLIT-Tablet on Allergic Rhinoconjunctivitis During Oak Pollen Season

Birch, alder, hazel, and oak are members of the birch homologous group based on cross-reactivity toward the birch pollen allergen Betula verrucosa 1. Theoretically, allergy to these tree pollens may be treated by immunotherapy with one representative allergen extract. To evaluate post hoc whether treatment of birch pollen-induced allergic rhinoconjunctivitis with a standardized tree sublingual immunotherapy (SLIT)-tablet containing birch pollen extract reduces symptoms and symptom-relieving medication use during the oak pollen season (OPS). In a randomized, multinational, double-blind trial (EudraCT-2015-004821-15), 634 participants (ages 12-65 years) received daily tree SLIT-tablet (12 SQ-Bet) or placebo before and during tree pollen season (alder/hazel plus birch pollen season [BPS]). Symptom-relieving medication was allowed. The primary end point was the average total combined score (sum of rhinoconjunctivitis daily symptom score and daily medication score) during BPS. Outcomes during the OPS (excluding overlapping BPS days) were analyzed post hoc. Relative improvements in average total combined score, daily symptom score, and daily medication score with the tree SLIT-tablet versus placebo during the OPS were 25%, 22%, and 32%, respectively (all P < .001). Significant correlations were observed between birch and oak serum immunoglobulin E (sIgE) at baseline (r= 0.86) and between birch and oak IgG4 after treatment (r= 0.72). Oak sIgE and IgG4 kinetics in response to tree SLIT-tablet treatment were similar to birch. The tree SLIT-tablet leads to significant improvement of rhinoconjunctivitis outcomes during the OPS, supporting the clinical relevance of immunological cross-reactivity toward birch and oak allergens.

Emergence of pollen food allergy syndrome in asthmatic children in Paris.

Over the last few decades, the level of pollen from birch and homologous trees has increased in parts of Europe. Sensitization to birch pollen allergens (principally Bet v 1) has been associated with food cross-reactivity called pollen food allergy syndrome (PFAS). To evaluate changes in allergic diseases due to IgE sensitization over 25years in asthmatic children. This was a cross-sectional retrospective study conducted in Paris. We analyzed two cohorts of asthmatic children with similar characteristics explored between 1993-1999 (old cohort=OC) and 2012-2018 (recent cohort=RC). 121 children were in the OC and 120 in the RC. An increase in sensitization to tree pollens was found especially for birch pollen, which was 11.6% in the OC and 31% in the RC (P=.0002). Allergic rhinitis prevalence was significantly higher in the RC than in the OC (96% vs 52%, respectively, P<.0001). IgE-mediated food allergy increased from 6% to 16% in the OC and RC, respectively, (P=.01) mainly due to PFAS. In the RC, a higher mean Bet v 1-specific IgE level was observed in children with PFAS compared to children without (105.7 KU/L±17.8 and 48.9 kU/L±15.7, respectively, P<.05). Allergic rhinitis and food allergy with tree pollen sensitization have increased in Paris over 25years mainly due to PFAS. Environmental factors could be responsible for these modifications as described in the literature.

Allergy to oak pollen in North America

Background: Oak pollen is an important allergen in North America. The genus Quercus (oak) belongs to the family Fagaceae under the order Fagales. Objective: The objective of this article was to narratively review the oak pollen season, clinical and epidemiologic aspects of allergy to oak pollen, oak taxonomy, and oak allergen cross-reactivity, with a focus on the North American perspective. Methods: A PubMed literature review (no limits) was conducted. Publications related to oak pollen, oak-related allergic rhinitis with or without conjunctivitis, and oak-related allergic asthma were selected for review. Results: Oak species are common throughout the United States and contribute up to 50% to overall atmospheric pollen loads. Mean peak oak pollen counts can reach >2000 grains/m³. The start of the oak pollen season generally corresponds to the seasonal shift from winter to spring based on latitude and elevation, and may begin as early as mid February. The duration of the season can last > 100 days and, in general, is longer at lower latitudes. In the United States, ∼30% of individuals with allergy are sensitized to oak. The oak pollen season correlates with increased allergic rhinitis symptom-relieving medication use and asthma-related emergency department visits or hospitalizations. Oak falls within the birch homologous group. Extensive immunologic cross-reactivity has been demonstrated between oak pollen and birch pollen allergens, and, more specifically, their major allergens Que a 1 and Bet v 1. The cross-reactivity between oak and birch has implications for allergy immunotherapy (AIT) because guidelines suggest selecting one representative allergen within a homologous group for AIT, a principle that would apply to oak. Conclusion: Allergy to oak pollen is common in North America and has a substantial clinical impact. Oak pollen allergens are cross-reactive with birch pollen allergens, which may have implications for AIT.

Patient management plan for sublingual allergen specific immunotherapy with birch pollen allergen and the maintenance of patient compliance

BACKGROUND:Sublingual allergen-specific immunotherapy (SLIT) inefficiencie is mainly caused by non-compliance with the treatment regimen and premature treatment termination.&#x0D; AIM:Frequency and causes of dropouts determination in children receiving SLIT with birch pollen according to the pre-coseasonal protocol, and approbation of the developed visit-to-visit patient management plan (Plan).&#x0D; MATERIALS AND METHODS:332 cases of treatment with birch pollen in children are analyzed. 290 patients (72.1% boys, aged 518 years (9.82 years [5.93; 14.67]), received SLIT with birch pollen in 20122019. 42 patients received SLIT according to the Plan (69% boys, 8.95 years old [5.38; 11.79]) in 20172019.&#x0D; RESULTS:A low dropout frequency was noted in the 1st and 2nd year of therapy (2 years after the start of treatment, 85% patients continue it). However, only 63.1% complete 3 years of therapy, and 11% 4 years of therapy. It has been shown that experienced allergists have more efficient patient retention. The implementation of the Plan increased patient retention in treatment at the 3rdyear of treatment up to 82.9% (p=0.02).&#x0D; CONCLUSION:The study confirmed the main reasons for the withdrawal of patients from SLIT: doubts about the effectiveness, cost and side effects. A low dropout frequency was shown according to the results of the 1stand 2ndyears of therapy, but only a small proportion of patients (11%) receive 4 or more courses of therapy. Visit-to-visit Plan optimizes the patients management, reduces patients withdrawal from treatment and can be recommended for practical healthcare.

IgE-reactivity profiles to allergen molecules in Russian children with and without symptoms of allergy revealed by micro-array analysis.

BackgroundThe analysis of longitudinal birth cohorts with micro‐arrayed allergen molecules has provided interesting information about the evolution of IgE sensitization in children. However, so far no cross‐sectional study has been performed comparing IgE sensitization profiles in children with and without symptoms of allergy. Furthermore, no data are available regarding molecular IgE sensitization profiles in children from Russia.MethodsWe recruited two groups of age‐ and gender‐matched children, one (Group 1: n = 103; 12.24 ± 2.23 years; male/female: 58/45) with symptoms and a second (Group 2: n = 97; 12.78 ± 2.23 years; male/female: 53/44), without symptoms of allergy according to international ISAAC questionnaire. Children were further studied regarding symptoms of allergy (rhinitis, asthma, atopic dermatitis) according to international guidelines, and skin prick testing with a panel of aeroallergen extracts was performed before sera were analyzed in an investigator‐blinded manner for IgE specific to more than 160 micro‐arrayed allergen molecules using ImmunoCAP ISAC technology.ResultsIgE sensitization = or >0.3 ISU to at least one of the micro‐arrayed allergen molecules was found in 100% of the symptomatic children and in 36% of the asymptomatic children. Symptomatic and asymptomatic children showed a comparable IgE sensitization profile; however, frequencies of IgE sensitization and IgE levels to the individual allergen molecules were higher in the symptomatic children. Aeroallergen sensitization was dominated by sensitization to major birch pollen allergen, Bet v 1, and major cat allergen, Fel d 1. Food allergen sensitization was due to cross‐sensitization to PR10 pollen and food allergens whereas genuine peanut sensitization was absent.ConclusionThis is the first study analyzing molecular IgE sensitization profiles to more than 160 allergen molecules in children with and without symptoms of allergy. It detects similar molecular IgE sensitization profiles in symptomatic and asymptomatic children and identifies Bet v 1 and Fel d 1 as the predominant respiratory allergen molecules and PR10 proteins as the major food allergens and absence of genuine peanut allergy in Moscow region (Russia).