[TWO CASES OF ALLERGIC VULVOVAGINITIS DIAGNOSED BY DIRECT MICROSCOPIC URINE SEDIMENT EXAMINATION].

Cedar pollen is known as a typical allergen that causes various allergic symptoms in the nasal mucosa, conjunctiva, and skin. However, inflammation of the vulvar mucosa due to sensitization to cedar pollen is not well-known. We experienced two cases in which the detection of cedar pollen during microscopic urine sediment examination led to the diagnosis of allergic vulvovaginitis caused by cedar pollen. The cases involved a 4-year-old girl and a 10-year-old girl. In both cases, the patients presented with chief complaints of pruritis in the vulva and insomnia due to frequent urination during the season of cedar pollen dissemination. Both patients were afebrile. No inflammatory skin changes such as erythema, swelling, or non-purulent discharge from mucous membranes of the vulva were observed. Microscopic urine sediment examination revealed large amounts of shed cedar pollen. The patients' conditions improved after treatment with oral antihistamines and instruction to dry their underwear indoors. Follow-up blood tests revealed high levels of specific anti-IgE antibodies to cedar pollen, thus confirming a diagnosis of allergic vulvovaginitis due to cedar pollen. Cedar pollen can cause allergic vulvovaginitis. Microscopic urine sediment examination is useful, and when combined with specific IgE antibody testing, leads to an appropriate diagnosis. This disease should also be considered in patients with complaints of vulvar discomfort during the season of cedar pollen dissemination.

Pollen and sub-pollen particles: External interactions shaping the allergic potential of pollen.

Pollen allergies, such as allergic rhinitis, are triggered by exposure to airborne pollen. They are a considerable global health burden, with their numbers expected to rise in the coming decades due to the advent of climate change and air pollution. The relationships that exist between pollens, meteorological, and environmental conditions are complex due to a lack of clarity on the nature and conditions associated with these interactions; therefore, it is challenging to describe their direct impacts on allergenic potential clearly. This article attempts to review evidence pertaining to the possible influence of meteorological factors and air pollutants on the allergic potential of pollen by studying the interactions that pollen undergoes, from its inception to atmospheric traversal to human exposure. This study classifies the evidence based on the nature of these interactions as physical, chemical, source, and biological, thereby simplifying the complexities in describing these interactions. Physical conditions facilitating pollen rupturing for tree, grass, and weed pollen, along with their mechanisms, are studied. The effects of pollen exposure to air pollutants and their impact on pollen allergenic potential are presented along with the possible outcomes following these interactions, such as pollen fragmentation (SPP generation), deposition of particulate matter on pollen exine, and modification of protein levels in-situ of pollen. This study also delves into evidence on plant-based (source and biological) interactions, which could indirectly influence the allergic potential of pollen. The current state of knowledge, open questions, and a brief overview of future research directions are outlined and discussed. We suggest that future studies should utilise a multi-disciplinary approach to better understand this complex system of pollen interactions that occur in nature.

[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.

Heterogeneity of sensitization profiles and clinical phenotypes among patients with seasonal allergic rhinitis in Southern European countries-The @IT.2020 multicenter study.

BACKGROUND: Pollen allergy poses a significant health and economic burden in Europe. Disease patterns are relatively homogeneous within Central and Northern European countries. However, no study broadly assessed the features of seasonal allergic rhinitis (SAR) across different Southern European countries with a standardized approach. OBJECTIVE: To describe sensitization profiles and clinical phenotypes of pollen allergic patients in nine Southern European cities with a uniform methodological approach. METHODS: Within the @IT.2020 multicenter observational study, pediatric and adult patients suffering from SAR were recruited in nine urban study centers located in seven countries. Clinical questionnaires, skin prick tests (SPT) and specific IgE (sIgE) tests with a customized multiplex assay (Euroimmun Labordiagnostika, Lübeck, Germany) were performed. RESULTS: Three hundred forty-eight children (mean age 13.1 years, SD: 2.4 years) and 467 adults (mean age 35.7 years SD: 10.0 years) with a predominantly moderate to severe, persistent phenotype of SAR were recruited. Grass pollen major allergenic molecules (Phl p 1 and/or Phl p 5) ranged among the top three sensitizers in all study centers. Sensitization profiles were very heterogeneous, considering that patients in Rome were highly poly-sensitized (sIgE to 3.8 major allergenic molecules per patient), while mono-sensitization was prominent and heterogeneous in other cities, such as Marseille (sIgE to Cup a 1: n = 55/80, 68.8%) and Messina (sIgE to Par j 2: n = 47/82, 57.3%). Co-sensitization to perennial allergens, as well as allergic comorbidities also broadly varied between study centers. CONCLUSIONS: In Southern European countries, pollen allergy is heterogeneous in terms of sensitization profiles and clinical manifestations. Despite the complexity, a unique molecular, multiplex, and customized in-vitro IgE test detected relevant sensitization in all study centers. Nevertheless, this geographical diversity in pollen allergic patients imposes localized clinical guidelines and study protocols for clinical trials of SAR in this climatically complex region.

Diagnosis and Management of Pollen Food Allergy Syndrome to Nuts.

Oral allergy syndrome or pollen food allergy syndrome (PFAS) represents a common clinical conundrum when the reported trigger food is a tree nut (usually almond or hazelnut) or peanut. The PFAS may give rise to uncertainty about the potential severity of the future reactions, indications for prescribing epinephrine, and the extent of the necessary dietary avoidance. As a food allergy, secondary to cross-reactivity with airborne pollen, PFAS usually manifests toward the end of the first decade of life as contact urticaria of the oropharyngeal mucous membranes. Molecular allergology facilitates diagnosis and risk stratification by establishing the profile of sensitization. Exclusive sensitization to pathogenesis-related proteins family 10 (PR10) and profilins indicates that signs and symptoms are due to PFAS, whereas sensitization to seed storage proteins with or without sensitization to PR10 and profilins may indicate a more severe primary nut allergy phenotype. Management relies on avoidance of the specific nut trigger, advice on the likelihood of more severe local or systemic symptoms, and treatment of reactions according to the severity. Future studies are needed to better delineate the risk of systemic reactions in individuals with nut PFAS and to establish the role of food or pollen allergen immunotherapy for the prevention or moderation of this condition.

Variations of pollen concentration in urban alleys of park city and the transmission pattern during the period of high allergenic risk: Taking Qingyang District of Chengdu City as an example.

Pollen (spores and pollen) allergy caused by green areas is one of the most serious environmental epidemics endangering urban public health. The pollen allergy rate in China reached 17.8% in 2022, characterized by a wide age range of onset, severity and diversity of symptoms. The aims of this study were to verify the consistency of the prediction results of pollen concentration and the index of allergenicity of urban green zones (IUGZA) equation, and to clarify the dispersal pattern of tree pollen in the urban alleys of cities with high density of static wind. We selected representative high, medium and low allergenic areas based on the allergenic stress in urban alleys of Qingyang District, Chengdu calculated by IUGZA equation, and monitored the pollen concentrations by selecting points and indicator species within the three allergenic areas. There was a consistency in the variation of pollen concentration in urban alleys of the three areas, with the highest pollen concentration in March. Mean pollen concentration showed a pattern of spring > autumn > summer > winter. The main pollen sources belonged to Ginkgo, Platanus, Firmiana and Cedrus, accounting for 42.4%, 16.3%, 9.0% and 6.5% of the total pollen, respectively. Wind speed had the greatest effect on pollen concentration and its dispersal distance in the urban alley. The horizontal dispersal distance of pollen was up to 260 m, and the number of pollen showed a significant negative linear correlation with the distance away from the pollen sources. The concentration of exotic pollen collected at the high site (4.5 m above ground) was much lower than that at the near-ground site (1.5 m above ground), but without difference in the types of pollen. The results of allergenic risk predicted by the IUGZA equation were consistent with the actual measured pollen concentration, which could be used in high-density static wind city.

Natural human Bet v 1-specific IgG antibodies recognize non-conformational epitopes whereas IgE reacts with conformational epitopes.

BACKGROUND: The nature of epitopes on Bet v 1 recognized by natural IgG antibodies of birch pollen allergic patients and birch pollen-exposed but non-sensitized subjects has not been studied in detail. OBJECTIVE: To investigate IgE and IgG recognition of Bet v 1 and to study the effects of natural Bet v 1-specific IgG antibodies on IgE recognition of Bet v 1 and Bet v 1-induced basophil activation. METHODS: Sera from birch pollen allergic patients (BPA, n = 76), allergic patients without birch pollen allergy (NBPA, n = 40) and non-allergic individuals (NA, n = 48) were tested for IgE, IgG as well as IgG1 and IgG4 reactivity to folded recombinant Bet v 1, two unfolded recombinant Bet v 1 fragments comprising the N-terminal (F1) and C-terminal half of Bet v 1 (F2) and unfolded peptides spanning the corresponding sequences of Bet v 1 and the apple allergen Mal d 1 by ELISA or micro-array analysis. The ability of Bet v 1-specific serum antibodies from non-allergic subjects to inhibit allergic patients IgE or IgG binding to rBet v 1 or to unfolded Bet v 1-derivatives was assessed by competition ELISAs. Furthermore, the ability of serum antibodies from allergic and non-allergic subjects to modulate Bet v 1-induced basophil activation was investigated using rat basophilic leukaemia cells expressing the human FcεRI which had been loaded with IgE from BPA patients. RESULTS: IgE antibodies from BPA patients react almost exclusively with conformational epitopes whereas IgG, IgG1 and IgG4 antibodies from BPA, NBPA and NA subjects recognize mainly unfolded and sequential epitopes. IgG competition studies show that IgG specific for unfolded/sequential Bet v 1 epitopes is not inhibited by folded Bet v 1 and hence the latter seem to represent cryptic epitopes. IgG reactivity to Bet v 1 peptides did not correlate with IgG reactivity to the corresponding Mal d 1 peptides and therefore does not seem to be a result of primary sensitization to PR10 allergen-containing food. Natural Bet v 1-specific IgG antibodies inhibited IgE binding to Bet v 1 only poorly and could even enhance Bet v 1-specific basophil activation. CONCLUSION: IgE and IgG antibodies from BPA patients and birch pollen-exposed non-sensitized subjects recognize different epitopes. These findings explain why natural allergen-specific IgG do not protect against allergic symptoms and suggest that allergen-specific IgE and IgG have different clonal origin.

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).

The perfect storm: temporal analysis of air during the world's most deadly epidemic thunderstorm asthma (ETSA) event in Melbourne.

BACKGROUND: There have been 26 epidemic thunderstorm asthma (ETSA) events worldwide, with Melbourne at the epicentre of ETSA with 7 recorded events, and in 2016 experienced the deadliest ETSA event ever recorded. Health services and emergency departments were overwhelmed with thousands requiring medical care for acute asthma and 10 people died. OBJECTIVES: This multidisciplinary study was conducted across various health and science departments with the aim of improving our collective understanding of the mechanism behind ETSA. DESIGN: This study involved time-resolved analysis of atmospheric sampling of the air for pollen and fungal spores, and intact and ruptured pollen compared with different weather parameters, pollution levels and clinical asthma presentations. METHODS: Time-resolved pollen and fungal spore data collected by Deakin AirWATCH Burwood, underwent 3-h analysis, to better reflect the 'before', 'during' and 'after' ETSA time points, on the days leading up to and following the Melbourne 2016 event. Linear correlations were conducted with atmospheric pollution data provided by the Environment Protection Authority (EPA) of Victoria, weather data sourced from Bureau of Meteorology (BOM) and clinical asthma presentation data from the Victorian Agency for Health Information (VAHI) of Department of Health. RESULTS: Counts of ruptured grass pollen grains increased 250% when the thunderstorm outflow reached Burwood. Increased PM10, high relative humidity, decreased temperature and low ozone concentrations observed in the storm outflow were correlated with increased levels of ruptured grass pollen. In particular, high ozone levels observed 6 h prior to this ETSA event may be a critical early indicator of impending ETSA event, since high ozone levels have been linked to increasing pollen allergen content and reducing pollen integrity, which may in turn contribute to enhanced pollen rupture. CONCLUSION: The findings presented in this article highlight the importance of including ruptured pollen and time-resolved analysis to forecast ETSA events and thus save lives.

Nasal IL-13 production identifies patients with late-phase allergic responses.

BACKGROUND: There is limited knowledge on how local cytokine secretion patterns after nasal allergen challenge correlate with clinical symptoms especially with regard to the "late allergic response," which occurs in approximately 40% to 50% of patients with allergy. OBJECTIVE: We sought to characterize the immunologic and clinical nasal responses to birch pollen allergen challenge with a special focus on the late allergic response. METHODS: In this randomized, double-blind, placebo-controlled trial, birch pollen-allergic participants were challenged with birch pollen extract (n = 20) or placebo (n = 10) on 3 consecutive days. On days 1 and 3, nasal secretions were collected at selected time points over a 24-hour time course for the measurement of 33 inflammatory mediators. Clinical responses were determined through subjective symptom scores and objective nasal airflow measurements. RESULTS: Provoked participants had significantly greater clinical responses and showed significant increases in tryptase and the soluble IL-33 receptor serum stimulation 2 (sST2) in nasal secretions within minutes compared with the placebo group. Eight of 20 provoked participants displayed high IL-13 levels 2 to 8 hours after allergen provocation. This group also showed significant changes in clinical parameters, with a secondary drop in nasal airflow measured by peak nasal inspiratory flow and increased symptoms of nasal obstruction, which significantly differed from IL-13 nonresponders after 6 hours. CONCLUSIONS: IL-13 response status correlates with clinical responses and type 2 cytokine responses in the late phase after allergen provocation.

A Pilot Study to Identify Grass Species That Mediate Pollen Allergy in Thailand.

INTRODUCTION: Some grass species that are either common or widely spread in Thailand have not been used for pollen allergy diagnosis. In order to improve diagnostic accuracy, the aim of this pilot study was to identify the grass species responsible for pollen allergy in Thailand. METHODS: The skin sensitization of pollen extracts from six different grass species, including rice (Oryza sativa), corn (Zea mays), sorghum (Sorghum bicolor), para grass (Urochloa mutica), ruzi grass (Urochloa eminii), and green panic grass (Megathyrsus maximus), was evaluated by skin prick test (SPT). Serum's IgE specific to each pollen extract was analyzed by Western blot (WB). The ImmunoCAPTM test for Johnson grass was also evaluated. RESULTS: Of the thirty-six volunteers who participated in this study, eighteen tested positive for at least one of the diagnostic tests, namely SPT, WB analysis, or ImmunoCAPTM. Notably, skin reactivity to para grass, corn, sorghum, and rice was more commonly observed compared to ruzi grass and green panic grass. However, in the WB analysis, individuals with pollen-specific IgE were more frequently detected in sorghum, green panic grass, corn, rice, and ruzi grass than para grass. CONCLUSION: In this pilot investigation, our findings indicate that the pollen extracts of rice, corn, sorghum, and para grass are associated with pollen allergy in Thailand. These results contribute to the current knowledge on the identification of grass species that are associated with pollen allergy in Thailand and Southeast Asia.

The Role of Defensins as Pollen and Food Allergens.

PURPOSE OF REVIEW: Defensin-polyproline-linked proteins are relevant allergens in Asteraceae pollen. Depending on their prevalence and amount in the pollen source, they are potent allergens, as shown for the major mugwort pollen allergen Art v 1. Only a few allergenic defensins have been identified in plant foods, such as peanut and celery. This review provides an overview of structural and immunological features, IgE cross-reactivity, and diagnostic and therapeutic options regarding allergenic defensins. RECENT FINDINGS: We present and critically review the allergenic relevance of pollen and food defensins. The recently identified Api g 7 from celeriac and other allergens potentially involved in Artemisia pollen-related food allergies are discussed and related to clinical severity and allergen stability. To specify Artemisia pollen-related food allergies, we propose the term "defensin-related food allergies" to account for defensin-polyproline-linked protein-associated food syndromes. There is increasing evidence that defensins are the causative molecules in several mugwort pollen-associated food allergies. A small number of studies have shown IgE cross-reactivity of Art v 1 with celeriac, horse chestnut, mango, and sunflower seed defensins, while the underlying allergenic molecule remains unknown in other mugwort pollen-associated food allergies. As these food allergies can cause severe allergic reactions, identification of allergenic food defensins and further clinical studies with larger patient cohorts are required. This will allow molecule-based allergy diagnosis and a better understanding of defensin-related food allergies to raise awareness of potentially severe food allergies due to primary sensitization to Artemisia pollen.

Pollen long-distance transport associated with symptoms in pollen allergics on the German Alps: An old story with a new ending?

Pollen grains are among the main causes of respiratory allergies worldwide and hence they are routinely monitored in urban environments. However, their sources can be located farther, outside cities' borders. So, the fundamental question remains as to how frequent longer-range pollen transport incidents are and if they may actually comprise high-risk allergy cases. The aim was to study the pollen exposure on a high-altitude location where only scarce vegetation exists, by biomonitoring airborne pollen and symptoms of grass pollen allergic individuals, locally. The research was carried out in 2016 in the alpine research station UFS, located at 2650 m height, on the Zugspitze Mountain in Bavaria, Germany. Airborne pollen was monitored by use of portable Hirst-type volumetric traps. As a case study, grass pollen-allergic human volunteers were registering their symptoms daily during the peak of the grass pollen season in 2016, during a 2-week stay on Zugspitze, 13-24 June. The possible origin of some pollen types was identified using back trajectory model HYSPLIT for 27 air mass backward trajectories up to 24 h. We found that episodes of high aeroallergen concentrations may occur even at such a high-altitude location. More than 1000 pollen grains m-3 of air were measured on the UFS within only 4 days. It was confirmed that the locally detected bioaerosols originated from at least Switzerland, and up to northwest France, even eastern American Continent, because of frequent long-distance transport. Such far-transported pollen may explain the observed allergic symptoms in sensitized individuals at a remarkable rate of 87 % during the study period. Long-distance transport of aeroallergens can cause allergic symptoms in sensitized individuals, as evidenced in a sparse-vegetation, low-exposure, 'low-risk' alpine environment. We strongly suggest that we need cross-border pollen monitoring to investigate long-distance pollen transport, as its occurrence seems both frequent and clinically relevant.

Relationship between IgE Levels Specific for Ragweed Pollen Extract, Amb a 1 and Cross-Reactive Allergen Molecules.

Ragweed (Ambrosia artemisiifolia) pollen is a major endemic allergen source responsible for severe allergic manifestations in IgE-sensitized allergic patients. It contains the major allergen Amb a 1 and cross-reactive allergen molecules, such as the cytoskeletal protein profilin, Amb a 8 and calcium-binding allergens Amb a 9 and Amb a 10. To assess the importance of Amb a 1, profilin and calcium-binding allergen, the IgE reactivity profiles of clinically well-characterized 150 ragweed pollen-allergic patients were analysed regarding specific IgE levels for Amb a 1 and cross-reactive allergen molecules by quantitative ImmunoCAP measurements, IgE ELISA and by basophil activation experiments. By quantifying allergen-specific IgE levels we found that Amb a 1-specific IgE levels accounted for more than 50% of ragweed pollen-specific IgE in the majority of ragweed pollen-allergic patients. However, approximately 20% of patients were sensitized to profilin and the calcium-binding allergens, Amb a 9 and Amb a 10, respectively. As shown by IgE inhibition experiments, Amb a 8 showed extensive cross-reactivity with profilins from birch (Bet v 2), timothy grass (Phl p 12) and mugwort pollen (Art v 4) and was identified as a highly allergenic molecule by basophil activation testing. Our study indicates that molecular diagnosis performed by the quantification of specific IgE to Amb a 1, Amb a 8, Amb a 9 and Amb a 10 is useful to diagnose genuine sensitization to ragweed pollen and to identify patients who are sensitized to highly cross-reactive allergen molecules present in pollen from unrelated plants, in order to enable precision medicine-based approaches for the treatment and prevention of pollen allergy in areas with complex pollen sensitization.

Ragweed is in the Air: Ambrosia L. (Asteraceae) and Pollen Allergens in a Changing World.

Globally Ambrosia species (Asteraceae), commonly called ragweed, are recognized to be one of the most problematic groups of invasive weeds and one of the main allergenic genus. Climate and land-use change and air pollution are expected to promote ragweed spread, increase airborne ragweed pollen concentrations (the source of allergens), extend the pollen season, and promote longdistance transport of pollen or sub-pollen particles containing allergens. The allergenicity of pollen itself is going to increase. Likely, all these factors will have meaningful effects in the exacerbation of the sensitization to ragweed pollen and the severity of allergy symptoms. Globally the major health concern regards A. artemisiifolia, because of its very wide global distribution and highly invasive behavior. Together with A. artemisiifolia, also A. trifida and A. psilostachya are species of health concern distributed across different continents, widespread and invasive in several regions. The present review summarizes the characteristics of these species and gives an overview of factors contributing to their allergenicity.

Ex Vivo Immunomodulatory Effects of Lactobacillus-, Lacticaseibacillus-, and Bifidobacterium-Containing Synbiotics on Human Peripheral Blood Mononuclear Cells and Monocyte-Derived Dendritic Cells in the Context of Grass Pollen Allergy.

Sensing of the intestinal microbiota by the host immune system is important to induce protective immune responses. Hence, modification of the gut microbiota might be able to prevent or treat allergies, mediated by proinflammatory Th2 immune responses. The aim was to investigate the ex vivo immunomodulatory effects of the synbiotics Pollagen® and Kallergen®, containing the probiotic bacterial strains Lactobacillus, Lacticaseibacillus and Bifidobacterium, in the context of grass pollen allergy. Peripheral blood mononuclear cells (PBMCs) from grass pollen-allergic patients and healthy controls were stimulated with grass pollen extract (GPE) and synbiotics and Gata3 expression and cytokine secretion analyzed. Monocyte-derived dendritic cells (MoDCs) cells were matured in the presence of GPE and synbiotics, co-cultured with autologous naïve T cells and maturation markers and cytokine secretion analyzed. GPE stimulation of PBMCs from grass pollen-allergic patients resulted in a significant higher production of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 compared to healthy controls. Gata3+CD4+ T cell induction was independent of the allergic status. The synbiotics promoted IL-10 and IFN-γ secretion and downregulated the GPE-induced Th2-like phenotype. Co-culturing naïve T cells with MoDCs, matured in the presence of GPE and synbiotics, shifted the GPE-induced Th2 cytokine release towards Th1-Th17-promoting conditions in allergic subjects. The investigated synbiotics are effective in downregulating the GPE-induced Th2 immune response in PBMCs from grass pollen-allergic patients as well as in autologous MoDC-T cell stimulation assays. In addition to increased IL-10 release, the data indicates a shift from a Th2- to a more Th1- and Th17-like phenotype.

RNA sequencing of single allergen-specific memory B cells after grass pollen immunotherapy: Two unique cell fates and CD29 as a biomarker for treatment effect.

BACKGROUND: Sublingual immunotherapy (SLIT) for grass pollen allergy can modify the natural history of allergic rhinitis and is associated with increased allergen-specific IgG4 . IgG4 competitively inhibits functional IgE on the surface of effector cells, such as mast cells and basophils, from binding to allergens. To further understand the important role memory B-cell (Bmem) responses play in mediating the beneficial effects of SLIT, we assessed changes in allergen-specific Bmem subsets induced by SLIT for grass pollen allergy. METHODS: Blood samples were collected twice outside the pollen season from twenty-seven patients with sensitization to ryegrass pollen (RGP; Lolium perenne) and seasonal rhinoconjunctivitis. Thirteen received 4-month pre-seasonal SLIT for grass pollen allergy, and 14 received standard pharmacotherapy only. Single-cell RNA sequencing was performed on FACS-purified Lol p 1-specific Bmem before and after SLIT from four patients, and significant genes were validated by flow cytometry on the total cohort. RESULTS: Four months of SLIT increased RGP-specific IgE and IgG4 in serum and induced two Lol p 1-specific Bmem subsets with unique transcriptional profiles. Both subsets had upregulated expression of beta 1 integrin ITGB1 (CD29), whereas IGHE (IgE), IGHG4 (IgG4 ), FCER2 (CD23), and IL13RA1 were upregulated in one subset. There was an increase in the proportion of Lol p 1+ Bmem expressing surface IgG4 , CD23, and CD29 after SLIT. CONCLUSIONS: A clinically successful 4 months course of SLIT for grass pollen allergy induces two transcriptionally unique Bmem fates. Associated changes in surface-expressed proteins on these Bmem subsets can be used as early biomarkers for treatment effects.

Atmospheric pollen allergen load and environmental patterns in central and southwestern Iberian Peninsula.

Over one quarter of the population in industrialised countries suffers from some type of allergy and inhaled aeroallergens from pollen are the primary cause of allergic ailments. The networks for monitoring biological air quality measure the airborne pollen concentrations that characterize periods of exposure to major airborne aeroallergens but there are certain discrepancies in relation to the allergen-pollen dynamic. In this paper we analyse the airborne allergens Ole e 1, Phl p 1, Phl p 5 and Pla a 1, and interpreted the adjustments and mismatches in their concentrations in relation to airborne pollen. The influence of main environmental patterns was considered. The study was conducted in two urban areas of the centre and southwest of the Iberian Peninsula (Toledo in Spain and Évora in Portugal). Monitoring for pollen followed the standard protocol using Hirst volumetric spore traps and allergenic particles were quantified by ELISA assay. The results indicate that the discrepancies in this relationship were affected by the weather conditions up to 6 days prior. Precipitation and humidity above normal values caused a higher concentration of the allergen Pla a 1. This effect occurred in reverse in the case of humidity for the allergens Ole e 1 and Phl p 1. Humidity and precipitation generated the same pattern in the allergen-pollen relationship in both Phl p 1 and Phl p 5. Our findings show consistent results that allow to interpret the rate of discrepancy between allergen and pollen, and it can be used to improve allergy risk prediction models generated from atmospheric pollen.

Outdoor Air Pollution and Indoor Window Condensation Associated with Childhood Symptoms of Allergic Rhinitis to Pollen.

Pollen is the main factor causing asthma and allergic rhinitis (AR). However, the key indoor and outdoor factors associated with childhood symptoms of allergic rhinitis (SAR) to pollen are unclear. We investigate the association of exposure to outdoor air pollution and indoor environmental factors with childhood SAR to pollen and consider SAR to pollen in different seasons. A cross-sectional study of 2598 preschool children aged 3-6 was conducted in Changsha, China (2011-2012). The prevalence of SAR to pollen in children and information on indoor environmental factors were obtained by questionnaire. Children's exposure to outdoor air pollutants (PM10, SO2, and NO2) was estimated from the monitored concentrations. The association of exposure to indoor environmental factors and outdoor air pollution with childhood SAR to pollen was estimated by multiple logistic regression models using odds ratio (OR) and a 95% confidence interval (CI), and the relationship between outdoor air pollutants and childhood SAR to pollen was investigated using restricted cubic splines. We found that early-life and current exposure to outdoor air pollution were significantly associated with childhood SAR to pollen in autumn, including exposure to SO2 one year before conception (OR = 1.60, 95% CI = 1.08-2.37) and during entire pregnancy (OR = 1.49, 95% CI = 1.01-2.20) periods, exposure to PM10 during the current period (OR = 1.78, 95% CI = 1.07-2.96), and exposure to NO2 during the early-life (one year before conception and entire pregnancy) and current periods with ORs (95% CI) of 1.72 (1.10-2.71), 1.82 (1.17-2.83), and 1.94 (1.11-3.40), respectively. Further, we found significant associations of both prenatal and postnatal exposure to window condensation with childhood SAR to pollen, with ORs (95% CI) = 1.37 (1.05-1.77) and 1.38 (1.02-1.88), respectively. We encourage SAR to pollen sufferers to stay indoors due to outdoor air pollution and higher pollen concentration outdoors, but indoor ventilation should be maintained.

Comparing available treatments for pollen-induced allergic rhinitis in children.

INTRODUCTION: Pollen-induced allergic rhinitis (PIAR) is a widespread disease in children, and its prevalence is rapidly evolving. In addition, it may be associated with other atopic diseases, in particular asthma. In most cases, PIAR can be treated effectively by avoiding exposure to responsible allergens and using symptomatic treatments, including intranasal/oral antihistamines or/and nasal corticosteroids, according to ARIA guidelines. In recent decades, new medicines have been studied and developed: allergen-specific immunotherapy (AIT), anti-IgE antibodies, and probiotics. In addition, nutraceuticals have also been used as add-on treatments. This review aims to discuss and compare the old and new therapeutic strategies for PIAR in children. AREAS COVERED: Allergic rhinitis is a type 2 inflammatory disease. The management of patients with PIAR entails medications, AIT, and ancillary therapies. In addition, children with PIAR and associated severe asthma may be inclusively treated with biologics. Namely, subjects with allergic comorbidities could benefit from biological agents. However, AIT presently remains the unique causal treatment for PIAR. EXPERT OPINION: New strategies may include combined treatments, mainly concerning fixed associations with antihistamines and corticosteroids, nutraceutical products, and new AIT formulations.