[Study on allergen components of birch pollen in Beijing area].

Objective:To explore the allergen components of birch pollen in the Beijing area and interpret its clinical significance. Methods:A total of 58 patients with birch pollen allergy were included in the cross-sectional study and divided into allergic rhinitis（AR） and allergic asthma（AA） groups according to clinical manifestations. Concentration of birch pollen allergen sIgE, as well as Bet v 1, Bet v 2, Bet v 4 and Bet v 6 sIgE were detected by ImmunoCAP immunolinked immunoassay. Differences of sIgE concentration of birch pollen allergen component in AR and AA were analyzed. Results:There were 44（75.9%） cases of AR and 14（24.1%） cases of AA were enrolled. All the 18 patients with spring pollen allergy were AR patients without AA. There were 40 cases with both spring and autumn pollen allergy, of which 26 cases（65%） were AR and 14 cases（35%） were AA. The sIgE of birch pollen allergen was level 2 or above in all subjects. 94.8% were positive for any four allergen components. 77.6% were mono-sensitized to any allergen component while 17.2% were dual-sensitized. The positive rate of Bet v 1 and/or Bet v 2 was 93.1%. The positive rates of four protein components were: Bet v 1（82.8%）, Bet v 2（29.3%）, Bet v 6（1.7%）, Bet v 4（0%）. sIgE of birch pollen was positively correlated with sIgE level of Betv 1（r=0.898, P<0.001）. The sIgE concentration of Bet v2 in AA group was significantly higher than that in AR group（[4.34±14.35] kUA/L vs [1.56±3.26] kUA/L, P<0.05）. There was no significant difference in other components. Conclusion:Bet v 1 is the main allergen component of birch pollen in the Beijing area, and Bet v 1 plus Bet v 2 can diagnose more than 90% of birch pollen allergy.

Allergenicity and structural properties of new Cor a 1 isoallergens from hazel identified in different plant tissues.

The hazel allergen Cor a 1 is a PR-10 protein, closely related to the major birch pollen allergen Bet v 1. Hazel allergies are caused by cross-reactive IgE antibodies originally directed against Bet v 1. Despite the importance of PR-10 proteins in allergy development, their function and localization in the plant remain largely elusive. Therefore, the presence of Cor a 1 mRNA and proteins was investigated in different tissues, i.e., the female flower, immature and mature nuts, catkins, and pollen. Four yet unknown Cor a 1 isoallergens, i.e., Cor a 1.0501-1.0801, and one new Cor a 1.03 variant were discovered and characterized. Depending on the isoallergen, the occurrence and level of mRNA expression varied in different tissues, suggesting different functions. Interestingly, Cor a 1.04 previously thought to be only present in nuts, was also detected in catkins and pollen. The corresponding Cor a 1 genes were expressed in Escherichia coli. The purified proteins were analysed by CD and NMR spectroscopy. Immunoblots and ELISAs to determine their allergenic potential showed that the new proteins reacted positively with sera from patients allergic to birch, hazel and elder pollen and were recognized as novel isoallergens/variants by the WHO/IUIS Allergen Nomenclature Sub-Committee.

rBet v 1a-BanLecwt induce upregulation of IL-10 and IFN-γ gene expression in Caco-2/THP-1 co-culture and secretion of IL-10 and IFN-γ/IL-4 levels in PBMCs of birch pollen allergic donors.

Novel allergen immunotherapy (AIT) approaches necessitate the use of more effective and safe therapeutics, which can be accomplished by employing novel adjuvants for improved innate immune cell activation, as well as hypoallergenic allergen forms. In this study, we investigate the immunomodulatory effects of a chimera rBet v 1a-BanLecwt (rBv1a-BLwt; Cwt) composed of the major birch pollen allergen Bet v 1a and banana lectin (BanLecwt; BLwt) and two novel chimeras, rBv1l-BLH84T (rBet v 1l-BanLecH84T; C1) and rBLH84T-Bv1l (rBanLecH84T-Bet v 1l; C2), both composed of BLH84T and hypoallergenic birch pollen allergen Bv1l in the co-culture model Caco-2/THP-1, and PBMCs from donors with birch pollen allergy. The chimeric molecules rBv1l-BLH84T (C1) and rBLH84T-Bv1l (C2) were created in silico and then produced in E. coli using recombinant DNA technology. Real-time PCR analysis of gene expression following compound treatment in the co-culture model revealed that all three chimeras have the potential to induce the anti-inflammatory cytokine IL-10 gene expression in Caco-2 cells and IFN-γ gene expression in THP-1 cells. Sandwich ELISA revealed that Cwt increased IL-10 secretion and IFN-/IL-4 levels in PBMCs from birch pollen allergic donors, whereas C1 and C2 were less effective. The findings suggest that Cwt should be analyzed further due to its potential benefit in AIT.

Endophytic fungi from Himalayan silver birch as potential source of plant growth enhancement and secondary metabolite production.

Mountain biodiversity is under unparalleled pressure due to climate change, necessitating in-depth research on high-altitude plant's microbial associations which are crucial for plant survival under stress conditions. Realizing that high-altitude tree line species of Himalaya are completely unexplored with respect to the microbial association, the present study aimed to elucidate plant growth promoting and secondary metabolite producing potential of culturable endophytic fungi of Himalayan silver birch (Betula utilis D. Don). ITS region sequencing revealed that the fungal isolates belong to Penicillium species, Pezicula radicicola, and Paraconiothyrium archidendri. These endophytes were psychrotolerant in nature with the potential to produce extracellular lytic activities. The endophytes showed plant growth promoting (PGP) traits like phosphorus solubilization and production of siderophore, indole acetic acid (IAA), and ACC deaminase. The fungal extracts also exhibited antagonistic potential against bacterial pathogens. Furthermore, the fungal extracts were found to be a potential source of bioactive compounds including the host-specific compound-betulin. Inoculation with fungal suspension improved seed germination and biomass of soybean and maize crops under net house conditions. In vitro PGP traits of the endophytes, supported by net house experiments, indicated that fungal association may support the growth and survival of the host in extreme cold conditions.

T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens.

Background: Allergens from Fagales trees frequently cause spring allergy in Europe, North America, and some parts of Asia. The definition of the birch homologous group, which includes birch (Bet v), oak (Que a), alder (Aln g), hazel (Cor a), hornbeam (Car b), beech (Fag s), and chestnut (Cas s), is based on high allergen sequence identity and extensive IgE cross-reactivity. Clinical effect was seen during the alder/hazel, birch, and oak pollen seasons after treatment with tree SLIT-tablets containing only birch allergen extract. Here, we characterize T-cell reactivity with respect to epitope specificities and cross-reactivity toward various Bet v 1 family members, (PR-10/group 1 major allergens). This cross-reactivity may be part of the immunological basis of clinical effect or cross-protection when exposed to birch homologous tree species. Method: T-cell lines were generated from 29 birch-allergic individuals through stimulation of peripheral blood mononuclear cells (PBMCs) with birch/Bet v or oak/Que a allergen extracts. T-cell responses to allergen extracts, purified group 1 allergens, and overlapping 20-mer peptides (Bet v 1, Aln g 1, Cor a 1, and Que a 1) were investigated by T-cell proliferation and cytokine production. Cross-reactivity was evaluated based on Pearson's correlations of response strength and further investigated by flow cytometry using tetramer staining for homologous peptide pairs. Results: T-cell reactivity toward extracts and group 1 allergens from across the birch homologous group was observed for birch/Bet v as well as oak/Que a T-cell lines. T-cell lines responded to multiple Bet v 1 homologous peptides from Aln g 1 and Cor a 1 and a subset of Que a 1 peptides. Significant Pearson's correlations between frequently recognized peptides derived from Bet v 1 and the corresponding peptides derived from alder, hazel, and oak strongly supported the T-cell cross-reactivity toward these allergens. Cross-reactivity between birch and birch homologous peptides was confirmed by pMHCII tetramer staining. Conclusion: T cells from birch tree pollen allergic individuals respond to multiple trees within the birch homologous group in accordance with the level of sequence homology between Bet v 1 family members, (PR-10 allergens) from these allergen sources, confirming the basis for clinical cross-protection.

Assessing IgE sensitization profiles to birch and timothy grass pollen allergens in birch pollen allergic blood donors using an oligoplex specific IgE assay.

IgE sensitization profiles to single birch allergens in birch-sensitized patients differ among European countries. The aim of this study was to determine the distribution of specific IgE antibodies to major and minor birch pollen allergens in a population of allergic Norwegian individuals by using a birch allergic blood donor population as a surrogate sample. Sixty blood donors were recruited and sampled based on birch allergy symptoms such as rhinitis, rhinoconjunctivitis and/or mild asthma in previous seasons. All sera were collected before start of the pollen season and tested using a line blot assay (Euroimmun AG, Lübeck, Germany) for IgE to birch and timothy pollen. Both extracts, single allergens, and cross-reacting carbohydrate determinants (CCD) were analysed. Only donors with specific IgE to birch and/or timothy grass were further evaluated. Specific IgE to birch pollen extract was found in 52 sera, and sensitization to timothy grass in 40 sera. Specific IgE to Bet v 1 was predominant in contrast to Bet v 4 which was absent. However, sensitization to the minor allergens Bet v 2 and 6 was always found together with high levels of IgE to Bet v 1. Subjects sensitized to the profilin Bet v 2 from birch were also sensitized to Phl p 12 from timothy grass. In conclusion, there was predominantly Bet v 1 sensitization in this cohort and low sensitization to minor allergens and cross-reactive allergens (Bet v 2, Bet v 4, Phl p 7 and Phl p 12).

Birch Bark Extract: A Review in Epidermolysis Bullosa.

Birch bark extract (Filsuvez®; also known as the developmental name Oleogel-S10), a topical gel consisting of 10% dry birch bark extract and 90% sunflower oil, is the first therapy approved in the EU and UK for the treatment of partial thickness wounds associated with dystrophic and junctional epidermolysis bullosa (EB) in patients aged ≥ 6 months old. In the pivotal double-blind, randomized, vehicle-controlled, phase III EASE trial in patients with EB, the primary endpoint was met, in which birch bark extract relative to control gel significantly increased the proportion of patients with first complete target wound closure within 45 days. Moreover, patients treated with birch bark extract demonstrated several other positive findings in improving wound burden and wound-associated symptoms. The clinical benefits of birch bark extract were maintained in the 24-month open-label extension period of the EASE trial. Birch bark extract was generally well tolerated in patients with EB, with the tolerability profile being similar to that of control gel. Current evidence indicates that birch bark extract is an effective, emerging treatment option for patients with dystrophic and junctional EB.

Epidermolysis bullosa (EB) is a rare, heterogenous genetic disorder characterized by extreme skin fragility and trauma-induced blister formation of the skin, mucosa or internal epithelial linings of organs. Due to lack of disease-modifying therapies, the mainstay treatment options for EB remain supportive in nature, such as wound care, skin protection, itch and pain management, infection control and trauma prevention. With various therapies being investigated as a potential treatment option for EB, birch bark extract (Filsuvez^®; also known as the developmental name Oleogel-S10) topical gel has been approved in the EU and UK for the treatment of partial thickness wounds associated with dystrophic and junctional EB in patients aged ≥ 6 months old. Birch bark extract has demonstrated anti-inflammatory, antibacterial, antiviral, antimycotic and wound-healing properties. In patients with EB, birch bark extract relative to control gel significantly accelerated wound healing within 45 days, together with other positive findings in improving wound burden and wound-associated symptoms. The clinical benefits of birch bark extract in improving wound burden were maintained for up to 24 months of continued treatment. Birch bark extract was generally well tolerated in patients with EB, with most adverse events being mild to moderate in severity. Current evidence indicates that birch bark extract is an effective, emerging treatment option for patients with dystrophic and junctional EB.

Circulating mast cell progenitors increase during natural birch pollen exposure in allergic asthma patients.

BACKGROUND: Mast cells (MCs) develop from a rare population of peripheral blood circulating MC progenitors (MCps). Here, we investigated whether the frequency of circulating MCps is altered in asthma patients sensitized to birch pollen during pollen season, compared to out of season. METHODS: Asthma patients were examined during birch pollen season in late April to early June (May), and out of season in November-January. Spirometry measurements, asthma and allergy-related symptoms, asthma control questionnaire (ACQ), and asthma control test (ACT) scores were assessed at both time points. The MCp frequency was determined by flow cytometry in ficoll-separated blood samples from patients with positive birch pollen-specific IgE, and analyzed in relation to basic and disease parameters. RESULTS: The frequency of MCps per liter of blood was higher in May than in November (p = .004), particularly in women (p = .009). Patients that reported moderate to severe asthma symptoms (<.0001), nose or eye symptoms (p = .02; p = .01), or reduced asthma control (higher ACQ, p = .01) had higher MCp frequency in May than those that did not report this. These associations remained significant after adjusting for sex and BMI. The change in asthma control to a lower ACT score in May correlated with an increase in MCp frequency in May (p = .006, rho = 0.46). CONCLUSIONS: The data suggest that the frequency of MCps increases in symptomatic patients with allergic asthma. Our results unravel a link between asthma symptoms and circulating MCps, and bring new insight into the impact of natural allergen exposure on the expansion of MCs.

Impact of meteorological parameters and air pollutants on airborne concentration of Betula pollen and Bet v 1 allergen.

The intensity of birch pollen season is expressed by seasonal pollen integral (SPIn, the sum of the mean daily pollen concentration during the birch pollination period) and the amount of Bet v 1 allergen released per birch pollen grain expressed by pollen allergen potency (PAP). Betula pollen and Bet v 1 allergen were simultaneously measured in the air of Bratislava from 2019 to 2022 by using two Burkard traps (Hirst-type and cyclone) in order to evaluate the causes of the seasonal variation in the SPIn and PAP levels. The highest SPIn (19,975 pollen/m3) was observed in 2022 and the lowest one (1484 pollen/m3) in 2021. The average daily PAP level (4.0 pg Bet v 1/pollen) was highest in 2019 and lowest (2.5 pg Bet v 1/pollen) in 2020. We found that seasonal variation in SPIn was associated mainly with the changes in environmental conditions during the pre-season period, whereas the year-to-year variation in PAP levels was attributed to environmental conditions during both pre- and in-season periods. Our results indicate that rainy weather in June 2020 and cold overcast weather in January‒February 2021 resulted in low SPIn in 2021. On the other hand, dry weather in June 2021 and warm weather in January‒February 2022 resulted in high SPIn in 2022. The low average daily PAP level in 2020 was associated with (1) low levels of gaseous air pollutants in March, when the ripening of pollen takes place; (2) an earlier start of the birch main pollen season (MPS); and (3) dry weather during the MPS. On the other hand, high PAP level in 2019 was associated with higher levels of air pollutants in March and during the MPS.

The History and Science of the Major Birch Pollen Allergen Bet v 1.

The term allergy was coined in 1906 by the Austrian scientist and pediatrician Clemens Freiherr von Pirquet. In 1976, Dietrich Kraft became the head of the Allergy and Immunology Research Group at the Department of General and Experimental Pathology of the University of Vienna. In 1983, Kraft proposed to replace natural extracts used in allergy diagnostic tests and vaccines with recombinant allergen molecules and persuaded Michael Breitenbach to contribute his expertise in molecular cloning as one of the mentors of this project. Thus, the foundation for the Vienna School of Molecular Allergology was laid. With the recruitment of Heimo Breiteneder as a young molecular biology researcher, the work began in earnest, resulting in the publication of the cloning of the first plant allergen Bet v 1 in 1989. Bet v 1 has become the subject of a very large number of basic scientific as well as clinical studies. Bet v 1 is also the founding member of the large Bet v 1-like superfamily of proteins with members-based on the ancient conserved Bet v 1 fold-being present in all three domains of life, i.e., archaea, bacteria and eukaryotes. This suggests that the Bet v 1 fold most likely already existed in the last universal common ancestor. The biological function of this protein was probably related to lipid binding. However, during evolution, a functional diversity within the Bet v 1-like superfamily was established. The superfamily comprises 25 families, one of which is the Bet v 1 family, which in turn is composed of 11 subfamilies. One of these, the PR-10-like subfamily of proteins, contains almost all of the Bet v 1 homologous allergens from pollen and plant foods. Structural and functional comparisons of Bet v 1 and its non-allergenic homologs of the superfamily will pave the way for a deeper understanding of the allergic sensitization process.

Pharmacotherapy and immunotherapy of allergic rhinitis induced by house dust mite, grass, and birch pollen allergens: a meta-analysis of randomized clinical trials.

BACKGROUND: The aim of this study was to assess the efficacy and safety of oral antihistamines (AHs), intranasal antihistamines (INAH) intranasal glucocorticosteroids (INCS), subcutaneous immunotherapy (SCIT), and sublingual immunotherapy (SLIT) in the management of allergic rhinitis (AR). The authors focused on the division into selected AR's triggers: house dust mites (HDMs), grass pollen, and birch pollen. METHODS: For each drug and allergen class, a meta-analysis of the efficacy and adverse events (AEs) was performed. The obtained results were presented as a therapeutic index (TIX-Score). RESULTS: Twenty-seven randomized clinical trials (RCTs) were included. The best total efficacy was observed for: HDMs for INCS and grass pollen for combination of INCS with INAH in a single device and for INAH. Considering the data that was obtained for birch pollen, SLIT showed statistically significant total efficacy. Summation scores for efficacy and AEs showed highest TIX-Score for combination of INCS and INAH in a single device in grass pollen. CONCLUSIONS: Treatment methods selected for this review may serve as an effective and safe treatment in reducing perennial and seasonal AR's symptoms. However, due to high heterogeneity probably associated with potential confounders existence in control in some cases, results should be interpreted with caution.

Diurnal pattern of Poaceae and Betula pollen flight in Central Europe.

In Central Europe the most common allergies are provoked by grass or birch pollen allergens. We determined the intra-daily behavior of airborne pollen grains of grasses (Poaceae) and birch (Betula ssp.) in Central Europe, based on data obtained from a network of automatic pollen monitors over Europe (www.pollenscience.eu). Our aim was to determine the time of day when the lowest concentrations occur, to provide allergic individuals the optimal time to ventilate their homes. The study was carried out in three Central European capitals, Berlin (Germany), Paris-Saclay (France), and Luxembourg (Luxembourg), as well as in eight stations in Germany (Altötting, Feucht, Garmisch-Partenkirchen, Hof, Marktheidenfeld, Mindelheim, Munich and Viechtach). The diurnal rhythm of these eleven locations was analyzed for either the complete, first week, peak week, peak day and last week of the pollen season. The data studied were reported as pollen/m3 measured in 3 h periods. Stations were classified as city, semi-populated or countryside areas using land-use and population density criteria. Grass pollen has a more pronounced diurnal rhythm than birch pollen concentrations. A significant difference was observed when comparing day (6-21 h) versus night (21-6 h) for all stations. No difference was detected between city and countryside for both pollen types, although for Poaceae a longer period of maximum concentrations was observed in big cities and higher day/night-time differences were registered in the countryside (6.4) than in cities (3.0). The highest pollen concentrations were observed between 9 and 18 h for grass, but the rhythm was less pronounced for birch pollen. For allergic individuals who want to bring in fresh air in their homes, we recommend opening windows after 21 h, but even better early in the morning between 6 and 9 h before pollinations (re)starts.

Comparison of Bioactive Secondary Metabolites and Cytotoxicity of Extracts from Inonotus obliquus Isolates from Different Host Species.

Inonotus obliquus, a wood-decaying mushroom, has been used as a health-promoting supplement and nutraceutical for centuries. It is a source of bioactive compounds accumulated in both the conks (pseudosclerotia/sclerotia) and the biomass obtained in vitro. This study aimed to qualitatively and quantitatively analyze the bioelements and selected metabolites produced in mycelial cultures obtained from different host species. The mycochemical potential of mycelial cultures isolated from pseudosclerotia grown in Betula pendula, Alnus glutinosa, and Carpinus betulus was compared. Parent cultures were obtained in two types of medium (malt extract agar substrates without and with birch wood). Experimental cultures were developed in 2 L bioreactors for 10 days. The content of bioelements was determined using FAAS and FAES methods. Organic compounds were estimated using the RP-HPLC-DAD method. The cytotoxicity of the extracts was evaluated in human keratinocytes HaCaT, human skin fibroblasts BJ, human liver cancer HepG2, human melanoma A375, and mouse melanoma B16-F10. The extracts showed the presence of bioelements: sodium, potassium, magnesium, calcium, zinc, manganese, iron, and copper; phenolic acids: p-hydroxybenzoic, caffeic, p-coumaric, and protocatechuic; sterols: lanosterol, ergosterol, ergosterol peroxide; triterpene compounds: betulin, betulinic acid, inotodiol; indole compounds: L-tryptophan, tryptamine, 5-methyltryptamine, melatonin. The content of bioactive substances in the biomass was dependent on both the origin of the host species of the fungus isolate and the type of culture medium. Based on the results of this study, mycelial cultures can be proposed as a potential source of bioactive compounds and are promising naturally derived cytotoxic agents.

Pollen Sensitization Can Increase the Allergic Reaction to Non-Cross-Reactive Allergens in a Soy-Allergic Patient.

During and after the pollen season, an increase in food-triggered allergic symptoms has been observed in pollen-food syndrome patients, possibly due to seasonal boosting of pollen-IgE levels. It has been suggested that consumption of birch-pollen-related foods plays a role in seasonal allergenic inflammation. However, whether this increased pollen sensitization during the pollen season can also affect the allergenicity of allergens that are non-cross-reactive with birch pollen remains in question. This study presents the case of a patient with soy allergy and pollinosis, who experiences worsening of gastrointestinal (GI) symptoms during the birch pollen season even though the eliciting food factor does not cross-react with birch pollen allergens and their homologs (e.g., Bet v 1 and Gly m 4). The results showed a notable increase in sIgE for Gly m 4 (3.3 fold) and Bet v 1 (2.6 fold) during the birch pollen season compared to outside the birch pollen season, while Gly m 5 and Gly m 6 showed only a slight increase (1.5 fold). The basophil activation test (BAT) showed that in this patient Gly m 5 and Gly m 6 are clinically relevant soy allergens, which correlates with the reported clinical symptoms to processed soy. Moreover, the BAT against raw soy shows an increase in basophil activation during the birch pollen season and a negative basophil activation result outside the birch pollen season. Thus, the worsening of GI symptoms could possibly be due to an increase in IgE receptors, an over-reactive immune system, and/or significant intestinal allergic inflammation. This case highlights the importance of including allergens that do not cross-react with birch pollen and using a functional assay such as the BAT to evaluate clinical relevance when assessing birch pollen seasonal influence on soy allergenicity.

Robbsia betulipollinis sp. nov., Isolated from Pollen of Birch (Betula pendula).

One gram-negative strain designated Bb-Pol-6 T was isolated from birch (Betula pendula) pollen at Giessen area, Germany. The analysis of 16S rRNA gene-based phylogenies indicated the next-relative genera were Robbsia, Chitinasiproducens, Pararobbsia and Paraburkholderia (96-95.6%). Further comparative genome analysis and phylogenetic tree-based methods revealed its phylogenetic position under the genus Robbsia. The genome of strain Bb-Pol-6 T was 5.04 Mbp with 4401 predicted coding sequences and a G + C content of 65.31 mol%. Average amino acid identity, average nucleotide identity, digital DNA-DNA hybridization and percentage of conserved proteins values to Robbsia andropogonis DSM 9511 T were 68.0, 72.5, 22.7 and 65.85%, respectively. Strain Bb-Pol-6 T was rod-shaped, non-motile, facultative anaerobic and grew optimally at 28 °C and pH 6-7. Ubiquinone 8 was the major respiratory quinone and the major cellular fatty acids were C16:0, C19:0 cyclo ω7c, C17:0 cyclo ω7c and C17:1 ω6c. The dominant polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminophospholipid. Based on the genomic physiological and phenotypic characteristics, strain Bb-Pol-6 T was considered a novel species under the genus Robbsia, for which the name Robbsia betulipollinis sp. nov. was proposed. The type strain is Bb-Pol-6 T (= LMG 32774 T = DSM 114812 T).

Pollen production of downy birch (Betula pubescens Ehrh.) along an altitudinal gradient in the European Alps.

High-altitude environments are highly susceptible to the effects of climate change. Thus, it is crucial to examine and understand the behaviour of specific plant traits along altitudinal gradients, which offer a real-life laboratory for analysing future impacts of climate change. The available information on how pollen production varies at different altitudes in mountainous areas is limited. In this study, we investigated pollen production of 17 birch (Betula pubescens Ehrh.) individuals along an altitudinal gradient in the European Alps. We sampled catkins at nine locations in the years 2020-2021 and monitored air temperatures. We investigated how birch pollen, flowers and inflorescences are produced in relation to thermal factors at various elevations. We found that mean pollen production of Betula pubescens Ehrh. varied between 0.4 and 8.3 million pollen grains per catkin. We did not observe any significant relationships between the studied reproductive metrics and altitude. However, minimum temperature of the previous summer was found to be significantly correlated to pollen (rs = 0.504, p = 0.039), flower (rs = 0.613, p = 0.009) and catkin (rs = 0.642, p = 0.005) production per volume unit of crown. Therefore, we suggest that temperature variability even at such small scales is very important for studying the response related to pollen production.

Intralymphatic immunotherapy with birch and grass pollen extracts. A randomized double-blind placebo-controlled clinical trial.

INTRODUCTION: There is a need to evaluate the safety and efficacy of intralymphatic immunotherapy (ILIT) for inducing tolerance in patients with allergic rhinitis. METHODS: Thirty-seven patients with seasonal allergic symptoms to birch and grass pollen and skin prick test >3 mm and/or IgE to birch and timothy >0.35 kU/L were randomized to either ILIT, with three doses of 0.1 mL of birch pollen and 5-grass pollen allergen extracts on aluminium hydroxide (10,000 SQ-U/ml; ALK-Abelló) or placebo using ultrasound-guided intralymphatic injections at monthly intervals. Daily combined symptom medical score and rhinoconjunctivitis total symptom score were recorded during the peak pollen seasons the year before and after treatment. Rhinoconjunctivitis total symptom score, medication score and rhinoconjunctivitis quality of life questionnaire were recorded annually starting 2 years after treatment. Circulating proportions of T helper cell subsets and allergen-induced cytokine and chemokine production were analysed using flow cytometry and ELISA. RESULTS: There were no differences between the groups related to daily combined symptom medical score the year before and after treatment. Two years after ILIT (after unblinding), the actively treated group reported significantly fewer symptoms, lower medication use and improved quality of life than did the placebo group. After the pollen seasons the year after ILIT, T regulatory cell frequencies and grass-induced IFN-γ levels increased only in the actively treated group. CONCLUSION: In this randomized controlled trial, ILIT with birch and grass pollen extract was safe and accompanied by immunological changes. Further studies are required to confirm or refute the efficacy of the treatment.

Allergen-free extracts from birch, ragweed, and hazel pollen activate human and guinea-pig submucous and spinal sensory neurons.

BACKGROUND: Non-allergenic, low molecular weight components of pollen grains are suspected to trigger changes in gut functions, sometimes leading to inflammatory conditions. Based on extensive neuroimmune communication in the gut wall, we investigated the effects of aqueous pollen extracts (APE) on enteric and spinal sensory neurons. METHODS: Using Ca2+ and fast potentiometric imaging, we recorded the responses of guinea-pig and human submucous and guinea-pig dorsal root ganglion (DRG) neurons to microejection of low (<3 kDa) and high (≥3 kDa) molecular weight APEs of birch, ragweed, and hazel. Histamine was determined pharmacologically and by mass spectrometry (LC-MS/MS). KEY RESULTS: Birch APE<3kDa evoked strong [Ca+2 ]i signals in the vast majority of guinea-pig DRG neurons, and in guinea-pig and human enteric neurons. The effect of birch APE≥3kDa was much weaker. Fast neuroimaging in human enteric neurons revealed an instantaneous spike discharge after microejection of birch, ragweed, and hazel APE<3kDa [median (interquartile range) at 7.0 Hz (6.2/9.8), 5.7 Hz (4.4/7.1), and 8.4 Hz (4.3/12.5), respectively]. The percentage of responding neurons per ganglion were similar [birch 40.0% (33.3/100.0), ragweed 50.8% (34.4/85.6), and hazel 83.3% (57.1/100.0)]. A mixture of histamine receptor (H1-H3) blockers significantly reduced nerve activation evoked by birch and ragweed APEs<3kDa , but was ineffective on hazel. Histamine concentrations in ragweed, birch and hazel APE's < 3 kDa were 0.764, 0.047, and 0.013 µM, respectively. CONCLUSIONS: Allergen-free APEs from birch, ragweed, and hazel evoked strong nerve activation. Altered nerve-immune signaling as a result of severe pollen exposure could be a pathophysiological feature of allergic and non-allergic gut inflammation.