Cross-reactive Pollen Research Articles

Identification of cross-reactive IgE-binding proteins from Philippine allergenic grass pollen extracts.

Respiratory allergies are one of the most common allergic diseases that affect Filipinos. Grass pollen accounts for the majority of the outdoor allergens triggering these respiratory allergies. Cross-reactivity among the Philippine grass pollen grains has not been extensively studied. This study aims to investigate the cross-reactivity of our local grasses and identify the cross-reactive allergens. Grass pollen grains were collected and processed into crude allergenic extracts. The IgE-reactivity of these crude allergenic pollen extracts was studied using sera from patients who tested positive for the mentioned extracts. The proteins from the immunoblots of cross-reactive pollen allergen extracts were sequenced and identified. Allergenic pollen proteins were identified as cross-reactive among the grass pollen extracts. Four of these have not been listed yet as grass allergens in the World Health Organization/International Union of Immunological Societies allergen nomenclature database. Local grass pollen allergens are cross-reactive with probable new allergens identified.

Food-Pollen Cross-Reactivity and its Molecular Diagnosis in China.

Plant-derived foods are one of the most common causative sources of food allergy in China, with a significant relationship to pollinosis. This review aims to provide a comprehensive overview of this food-pollen allergy syndrome and its molecular allergen diagnosis to better understand the cross-reactive basis. Food-pollen cross-reactivity has been mainly reported in Northern China, Artemisia pollen is the major related inhalant source, followed by tree pollen (Betula), while grass pollen plays a minor role. Pollen allergy is relatively low in Southern China, with allergies to grass pollen being more important than weed and tree pollens. Rosaceae fruits and legume seeds stand out as major related allergenic foods. Non-specific lipid transfer protein (nsLTP) has been found to be the most clinically relevant cross-reacting allergenic component, able to induce severe reactions. PR-10, profilin, defensin, chitinase, and gibberellin-regulated proteins are other important cross-reactive allergen molecules. Artemisia pollen can induce allergenic cross-reactions with a wide range of plant-derived foods in China, and spring tree pollens (Betula) are also important. nsLTP found in both pollen and plant-derived food is considered the most significant allergen in food pollen cross-reactivity. Component-resolved diagnosis with potential allergenic proteins is recommended to improve diagnostic accuracy and predict the potential risk of causing allergic symptoms.

The role of short-term grass pollen exposure in food skin-prick test reactivity, food allergy, and eczema flares in children.

While the relationship between pollen and respiratory allergies is well-documented, the role of short-term pollen exposure in food allergy and eczema flares has not previously been explored. We aimed to investigate these associations in a population-based sample of children. We investigated 1- (n=1108) and 6-year-old (n=675) children in the grass pollen season from the HealthNuts cohort. Grass pollen concentrations were considered on the day of testing (lag 0), up to three days before (lag 1-lag 3) and cumulatively (lag 0-3). Associations between grass pollen and food skin-prick test reactivity (SPT ≥ 2 mm at age 1year and ≥ 3 mm at age 6 years), eczema flares, challenge-confirmed food allergy, reaction threshold to oral food challenges (OFC), and serum food-specific IgE levels were analyzed using either logistic or quantile regression models. Atopy and family history of allergic disease were considered as potent effect modifiers. Grass pollen at lag 0-3 (every 20 grains/m3 increase) was associated with an up to 1.2-fold increased odds of food SPT reactivity and eczema flares in 6-year-olds. In 1-year-olds, the associations were only observed for peanut in those with a family history of food allergy. Increasing grass pollen concentrations were associated with a lower reaction threshold to OFC and higher serum IgE levels in peanut-allergic 1-year-olds only. Increasing grass pollen concentration was associated with increased risk of food SPT reactivity and eczema flares in children. The associations in peanut-allergic infants may be related to immune activation and/or peanut and grass pollen cross-reactivity leading to a lower reaction threshold.

Anaphylaxis across Europe: are pollen food syndrome and lipid transfer protein allergy so far apart?

Traditionally pollen-food syndrome (PFS) is considered to be a mild cross-reacting food allergy affecting only Northern Europe, with lipid transfer protein (LTP) allergy being more severe and mainly occurring in Southern Europe. This review seeks to update the reader on both types of plant food allergy and to determine whether the stereotypical presentations of these plant food allergies remain the same, with a particular focus on reaction severity. Recent findings suggest that both these types of plant food allergy occur in children and adults. Although it is true that PFS allergy is more prevalent in Northern Europe and LTP allergy is more well known in Southern Europe, these conditions are not hidebound by geography, and the increasing spread and allergenicity of pollen due to global warming continues to change their presentation. Both conditions have a spectrum of symptom severity, with PFS sometimes presenting with more severe symptoms, including anaphylaxis and LTP allergy with milder reactions. It is important to consider that in many parts of Europe, reactions to plant foods, especially fruits or vegetables, could be mediated either by pollen cross-reactivity or primary sensitization to LTP allergens. All those presenting with symptoms to plant foods will benefit from a detailed clinical history and appropriate tests so that an accurate diagnosis can be made, and correct management implemented.

Development of mouse model for oral allergy syndrome to identify IgE cross-reactive pollen and food allergens: ragweed pollen cross-reacts with fennel and black pepper.

Oral allergy syndrome (OAS) is an IgE-mediated immediate food allergy that is localized to the oral mucosa. Pollen food allergy syndrome (PFAS), a pollinosis-associated OAS, is caused by cross-reactivity between food and pollen allergens. However, we need to more precisely understand the underlying pathogenesis of OAS/PFAS. In the present study, we developed a method to comprehensively identify cross-reactive allergens by using murine model of OAS and protein microarray technology. We focused on lip angioedema, which is one of the most common symptoms of OAS, and confirmed that mast cells reside in the tissues inside the lower lip of the mice. Interestingly, when the food allergen ovalbumin (OVA) was injected inside the lower lip of mice with high levels of OVA-specific IgE followed by an intravenous injection of the Evans blue dye, we found immediate dye extravasation in the skin of the neck in a mast cell-dependent manner. In addition, the degree of mast cell degranulation in the oral cavity, reflecting the severity of oral allergic responses, can be estimated by measuring the amount of extravasated dye in the skin. Therefore, we used this model of OAS to examine IgE cross-reactive allergens in vivo. Protein microarray analysis showed that serum IgE from mice intraperitoneally sensitized with ragweed pollen, one of the major pollens causing pollinosis, bound highly to protein extracts from several edible plants including black peppercorn and fennel. We confirmed that the levels of black pepper-specific IgE and fennel-specific IgE were significantly higher in the serum from ragweed pollen-sensitized mice than in the serum from non-sensitized control mice. Importantly, analysis of murine model of OAS showed that the injection of black pepper or fennel extract induced apparent oral allergic responses in ragweed pollen-sensitized mice. These results indicate IgE cross-reactivity of ragweed pollen with black pepper and fennel. In conclusion, we developed mouse model of OAS to identify IgE cross-reactive pollen and food allergens, which will help understand the pathogenesis of OAS/PFAS.

Assessing cross-reactivity in allergen immunotherapy.

Knowledge of patterns of pollen cross-reactivity is crucial for formulation of immunotherapy vaccines. As phylogenetic relationships have become better clarified through the use of tools such as gene sequencing, it is apparent that cross-reactivity reflects taxonomy in the vast majority of cases. Contradictory observations of unexpected cross-reactivity between distantly related plants require explanation. There are many proteins, presumably performing vital functions, tightly preserved throughout the evolutionary tree from plants to animals. Examples are profilins, lipid transfer proteins, and pathogenesis-related proteins. These may function as panallergens. The small differences that exist between these ubiquitous proteins may explain why these are frequently minor allergens, not reacting in the majority of allergic sera. This article summarizes cross-reactivity from older studies using crude pollen extracts as well as newer research of purified or recombinant allergenic proteins. The patterns of cross-allergenicity that emerge should be helpful in guiding therapeutic decisions.

What is the role of allergen immunotherapy in IgE-mediated food allergy?

In food allergy, allergen avoidance and emergency treatment are still therapeutic hallmarks but, recently, allergen immunotherapy (AIT), with different application routes, has gained more attention. In primary food allergy, oral immunotherapy has been frequently used in clinical trials. This year, an oral immunotherapy preparation for treatment of peanut allergy was licensed in Europe. In secondary food allergy, sublingual and subcutaneous extracts have been used in clinical trials, mostly with cross-reactive pollen allergens. As there is no AIT preparation licensed for this indication, therapy should only be started when there also is aneed for treating associated respiratory symptoms.

Antigenic cross-reactivity between Schistosoma mansoni and pollen allergens from the birch tree (Betula verrucosa) and Timothy grass (Phleum pratense): involvement of shared glycan epitopes and implications for the hygiene hypothesis

Previous studies have shown that schistosome infection can protect against allergic symptoms, but the underlying mechanisms are still not fully understood. Here we have shown that rabbit IgG antibodies raised against Schistosoma mansoni soluble egg antigens (SmSEA) are cross-reactive with a wide array of molecules in Timothy grass pollen (TGP) and birch tree pollen (BTP). Five of the cross-reactive pollen molecules (two from TGP and three from BTP) were selected randomly and identified by tandem mass spectrometric (TMS) analysis to be, respectively, the TGP allergens Phl p 1 and Phl p 5b, and BTP glutathione S-transferase (GST), and the BTP allergens Bet v 1 and Bet v 6.0102. Rabbit anti-SmSEA IgG antibodies that cross-reacted with each of the five allergens were found to be reactive with three major S. mansoni egg antigens, IPSE/alpha-1, omega-1 and kappa-5. Pairwise alignment of the amino acid sequences of each of the five TMS-identified pollen allergens with each of the three egg antigens revealed a low level of amino acid sequence identity. Further experiments indicated that the schistosome antigen/allergen cross-reactivity was mostly due to similar glycans present in helminths and plants, but not in mammals: so called cross-reactive carbohydrate determinants (CCDs). Previously, CCDs have been implicated in the cross-reactivity between many plants and invertebrates. Furthermore, pollen-induced anti-CCD IgGs have been found in sera of patients undergoing allergen-specific immunotherapy (SIT) and implicated in the treatment of the allergy. Thus, our finding provides not only possible explanations for the allergy-protective effect of helminth/schistosome infections as explained by the hygiene hypothesis, but also a potential starting point for improved SIT.

Pollen-related food allergy: an update

The vast majority of IgE-mediated food allergies in adults are based on sensitization to pollen, followed by reactions to structurally related, often unstable allergens, in particular in fruit (including edible nuts), vegetables, and spices. This article provides an up-to-date overview of selected scientific works on pollen-related food allergy and has been drawn-up on the basis of PubMed research, the German Study on Adult Health (Studie zur Gesundheit Erwachsener in Deutschland, DEGS) conducted by the Robert Koch Institute, as well as the national and international guideline registries. Birch pollen-related symptoms are generally the commonest form of pollen-related allergy observed in Northern Europe. The types of fruit that most frequently cause symptoms belong to the Rosaceae (e. g., apple, cherry) and Fagales families (hazelnut). Reactions to legumes (e. g., peanut, soy) and vegetables, including celery, carrot, tomato, and bell pepper, are also worthy of note. In addition to oropharyngeal contact urticaria, the clinical symptoms of pollen-related food allergy can range from the involvement of other organ systems to anaphylactic shock. The main plant food allergens belong to a handful of protein families: Bet v 1 homologs, profilins, lipid transfer proteins, storage proteins, and thaumatin-like proteins. The diagnosis of pollen-related food allergy has seen significant advances in recent years in the wake of component-resolved/molecular allergology, thereby, enabling reliable identification. Treatment comprises dietary counseling and the prescription of emergency medication. In addition, allergen-specific immunotherapy for cross-reactive pollen allergens appears to positively affect concomitant food allergies in some patients.

Allergen of the Month—Annual Wormwood

Allergen of the Month—Annual Wormwood

Food sensitisation profiles in school‐aged children from China and Russia

Shrimp (7-25%) and crab (4-9%) were the most common food sensitizations in Chinese children, except in Hong Kong, where egg (17%) and milk (15%) sensitization was higher than that to shrimp (13%). In all other sites <7% was sensitized to milk and egg. Children from Tomsk were mostly sensitized to hazelnuts and fruits (~6%) and this was associated with birch pollen and Bet v 1 sensitization. Hazelnut sensitization was <4% in China and fruit sensitization was almost absent in Guangzhou. Sensitization to house dust mite (HDM) was exceptionally high in China (p39%), especially in Hong Kong (73%), compared to Tomsk (13%). IgE titers to HDM were significantly lower in Shaoguan (median 2.0 kUA/L) than in Hong Kong and Guangzhou (median 71.8 and 26.2 kUA/L, respectively). Conclusion Sensitization profiles in Tomsk are dominated by birch pollen cross-reactivity, similar to what is common in Central and Northern Europe. In contrast, sensitization to HDM and sea foods dominated the picture in China. Whether house dust mite sensitization is (partly) at the basis of the high prevalence of seafood sensitization (e.g. via Der p 10/tropomyosin) or whether it is the seafoodrich diet, is currently under investigation.

Hazelnut allergy across Europe dissected molecularly: A EuroPrevall outpatient clinic survey

Hazelnut allergy is birch pollen-driven in Northern/Western Europe and lipid transfer protein-driven in Spain and Italy. Little is known about other regions and other allergens. Establishing a molecular map of hazelnut allergy across Europe. In 12 European cities, subjects reporting reactions to hazelnut (n = 731) were evaluated and sensitization to 24 foods, 12 respiratory allergen sources, and latex was tested by using skin prick test and ImmunoCAP. A subset (124 of 731) underwent a double-blind placebo-controlled food challenge to hazelnut. Sera of 423 of 731 subjects were analyzed for IgE against 7 hazelnut allergens and cross-reactive carbohydrate determinants by ImmunoCAP. Hazelnut allergy was confirmed in 70% of those undergoing double-blind placebo-controlled food challenges. Birch pollen-driven hazelnut sensitization (Cor a 1) dominated in most cities, except in Reykjavik, Sofia, Athens, and Madrid, where reporting of hazelnut allergy was less frequent anyhow. In Athens, IgE against Cor a 8 dominated and strongly correlated with IgE against walnut, peach, and apple and against Chenopodium, plane tree, and mugwort pollen. Sensitization to seed storage proteins was observed in less than 10%, mainly in children, and correlated with IgE to nuts, seeds, and legumes. IgE to Cor a 12, observed in all cities (10% to 25%), correlated with IgE to nuts, seeds, and pollen. In adulthood, the importance of hazelnut sensitization to storage proteins, oleosin (Cor a 12), and Cor a 8 is diluted by the increased role of birch pollen cross-reactivity with Cor a 1. Cor a 8 sensitization in the Mediterranean is probably driven by diet in combination with pollen exposure. Hazelnut oleosin sensitization is prevalent across Europe; however, the clinical relevance remains to be established.

PROPERTIES OF POLLEN ALLERGENS AND THEIR CLINICAL SIGNIFICANCE

Pollen, the male gametophyte of flowering plant species, is one of the most predominant sources of environmental allergens, and a significant cause of allergic disease. This review discusses the nature of pollen proteins as allergens, their effect on the human immune system. The influence of cross-reactive pollen allergens to the incidence of food sensitivities is also discussed. Flowering plant species that posses allergenic pollen, identified with allergens cloned from these species, are also discussed.

P91 ‐ Pilot study on sensitisation profiles of children with a primary tree nut allergy

Background Plant food allergy is a relatively frequent medical problem in childhood. Peanut and tree nuts are the most common causes. Some are allergic to tree nuts due to pollen cross reactivity whereas others have a primary tree nut allergy. Cross sensitivity is also seen between tree nuts and is serologically well described. But the clinical picture of cross sensitivity amongst tree nut allergic children is less investigated.

Profilin cross-reactive panallergen causes latex sensitization in the pediatric population allergic to pollen

BackgroundComponent-resolved diagnostics (CRD) has been demonstrated to be an excellent new tool for improving the current diagnosis of allergies, and it allows differentiation between polysensitization and cross-reactivity. ObjectiveTo demonstrate the role of cross-reactive pollen allergens in pediatric patients living in areas with large amounts of airborne grass pollen grains who are sensitive to grass pollen and latex. MethodsSerum samples were obtained from 106 children between 3 and 14 years of age diagnosed with allergies to pollen based on clinical history, skin prick tests, and specific immunoglobulin E (IgE). None of them had allergy symptoms to latex or fruits. From these 106 children, 56 patients revealed positive results to Phleum-specific major allergens but not to cross-reactive allergens. The other 50 patients who showed positive specific IgE to Phleum-specific major allergens and to cross-reactive pollen allergens also showed positive results to latex allergens. CRD was carried out by specific IgE quantification using a fluoro-enzyme immunoassay (ImmunoCAPT System). ResultsResults demonstrated a positive significant relationship between the specific IgE to Hev b 8 and Phl p 12 and also between the specific IgE to Hev b 8 and latex extract in the group of patients sensitized to species-specific and cross-reactive Phleum allergens. Positive significant relationships were also found between profilin and avocado or peach sensitizations. No other latex allergens gave positive results. ConclusionThe apparent sensitization to latex in pediatric patients allergic to grass pollen is caused by the cross-reactive profilin panallergen; however, it is appears not to be clinically relevant.

Cross-reactivity of pollen and food allergens: soybean Gly m 4 is a member of the Bet v 1 superfamily and closely resembles yellow lupine proteins

In many cases, patients allergic to birch pollen also show allergic reactions after ingestion of plant-derived food. This observation is explained on the molecular level by cross-reactivity of IgE antibodies induced by sensitization to the major birch pollen allergen Bet v 1 with homologous food allergens. As IgE antibodies recognize conformational epitopes, a precise structural characterization of the allergens involved is necessary to understand cross-reactivity and thus to develop new methods of allergen-specific immunotherapy for allergic patients. Here we present the three-dimensional solution structure of the soybean allergen Gly m 4, a member of the superfamily of Bet v 1 homologous proteins and a cross-reactant with IgE antibodies originally raised against Bet v 1, as shown by immunoblot inhibition and histamine release assays. Although the overall fold of Gly m 4 is very similar to that of Bet v 1, the three-dimensional structures differ in detail. The Gly m 4 local structures that display those differences are also found in proteins from yellow lupine. The three-dimensional structure of Gly m 4 in combination with immunological data allows us to propose surface patches that might represent cross-reactive epitopes.

Soy, milk and wheat allergy

Food allergies affect 5-10% of infants, 2-5% of toddlers, and 1.3-2.6% of school children in Japan. Egg, milk and wheat are the major three food allergens. Soybean is one of the eight foods causing immediate allergic reactions, sometimes anaphylaxis. Fermented soybeans, miso and shoyu, are used in most of the traditional Japanese foods, and exposure to soybeans in Japanese children begins as one of the first solid foods, typically in the form of tofu. Sensitization to soy, milk and wheat occurs in many atopic babies. Some are the primary sensitizations to the foods through oral or cutaneous route, but others may be the secondary sensitization through cross-reactive foods or pollens. Component-specific IgE tests provide us more sensitive and specific diagnostic tools. We have found that casein, one of the most classically known allergen components in milk, can be a more specific marker in the diagnosis of milk allergy, especially in the older children. Recombinant ω-5 gliadin ImmunoCAP® provides almost 100 % positive predictive value of immediate type wheat allergy in children at 17.5 kUA/L, as well as wheat-dependent exercise-induced anaphylaxis in adults. Gly m 5 and Gly m 6 from soybean can be a marker of severe primary soy allergy in Japanese children. On the other hands, patients with secondary soy allergy in adults, who have allergic reactions exclusively to soy milk, but not to tofu, are predominantly sensitized to Gly m 4 (PR-10), possibly due to the cross-reactive pollen allergens. In conclusion, allergen component testing is an excellent clinical tool from a diagnostic point of view but also provide us with new insights into food allergy.

Association of allergic patients’ phenotypes with IgE reactivity to recombinant pollen marker allergens

During the last decade allergen molecules from several allergen sources have been produced by recombinant DNA technology. The aim of this study was to investigate whether IgE reactivity to recombinant pollen allergens with broad and narrow cross-reactivity is associated with clinical phenotypes of allergic sensitization. Serum IgE reactivity to a panel of six recombinant birch and grass pollen allergens was measured by ELISA in pollen sensitized patients from Central Europe to define groups of patients with exclusive IgE reactivity to rBet v 1, with exclusive reactivity to major grass pollen allergens (rPhl p 1, rPhl p 2, rPhl p 5) and with IgE reactivity to cross-reactive pollen allergens (rBet v 2, rPhl p 7). Patients' clinical phenotypes were recorded. IgE responses to tree, grass and weed pollen as well as plant food extracts were evaluated in vitro by CAP-FEIA and clinical sensitivities were confirmed in vivo by skin prick testing. IgE reactivity to the recombinant major birch pollen allergen, rBet v 1, was associated with sensitization to pollen from birch, taxonomically related trees and to certain plant-derived food. Reactivity to the recombinant timothy grass pollen allergens, rPhl p 1, rPhl p 2, rPhl p 5, indicated sensitization to pollen from grasses. Patients reacting with the highly cross-reactive allergen rPhl p 7 were polysensitized to pollen from unrelated trees, grasses and weeds and rBet v 2-positive patients were polysensitized to pollen and plant-derived food from unrelated plants. IgE reactivity to recombinant marker allergens is associated with clinical phenotypes of allergic sensitization and may be useful for the selection of treatment strategies.

Cross-reactivity of pollen and food allergens: soybean Gly m 4 is a member of the Bet v 1 superfamily and closely resembles yellow lupine proteins

In many cases, patients allergic to birch pollen also show allergic reactions after ingestion of certain fruits or vegetables. This observation is explained at the molecular level by cross-reactivity of IgE antibodies induced by sensitization to the major birch pollen allergen Bet v 1 with homologous food allergens. As IgE antibodies recognize conformational epitopes, a precise structural characterization of the allergens involved is necessary to understand cross-reactivity and thus to develop new methods of allergen-specific immunotherapy for allergic patients. Here, we report the three-dimensional solution structure of the soybean allergen Gly m 4, a member of the superfamily of Bet v 1 homologous proteins and a cross-reactant with IgE antibodies originally raised against Bet v 1 as shown by immunoblot inhibition and histamine release assays. Although the overall fold of Gly m 4 is very similar to that of Bet v 1, the three-dimensional structures of these proteins differ in detail. The Gly m 4 local structures that display those differences are also found in proteins from yellow lupine with known physiological function. The three-dimensional structure of Gly m 4 may thus shed some light on the physiological function of this subgroup of PR10 proteins (class 10 of pathogenesis-related proteins) and, in combination with immunological data, allow us to propose surface patches that might represent cross-reactive epitopes.

Cross-reactivity of pollen allergens: recommendations for immunotherapy vaccines

This review will summarize recent research on pollen allergen and epitope cross-reactivity. Knowledge of these relationships aids in the rational formulation of allergen immunotherapy vaccines. There has been further clarification of panallergens and their roles as both major and minor allergens. Recent studies have targeted non-specific lipid transfer proteins and calcium-binding proteins (polcalcins), as well as pathogenesis-related protein families and profilins. Polcalcins and non-specific lipid transfer proteins are responsible for pollen-fruit interactions as well as pollen cross-reactivity, in some cases, but not all, accounting for major allergenicity. Delineation of the enzymatic activity of certain allergens explains the ubiquitous nature of these pollen proteins. Characterization of specific pollen allergens and their protein families has provided insight into the grounds for cross-reactivity. Continuing clarification of these relationships will allow the substitution and consolidation of inhalant extracts as described in the conclusion.