Bet v 1
Summary
Bet v 1 is a heat labile protein with a molecular weight of 17.5 kDa belonging to the PR-10 protein family. It is the major allergen of birch pollen. Up to 95% of birch pollen allergic patients have been reported to be sensitized to Bet v 1. Sensitization is prevalent in regions with birch pollen exposure, including Europe, North America and parts of Asia. In Europe, the lowest prevalence was observed in Portugal (6.8%) and the highest in Denmark (57.4%). Sensitization to Bet v 1 has been reported as a predictor of allergic rhinitis and asthma. There is extensive IgE cross-reactivity between Bet v 1 and pollen allergens from other Fagales trees such as hazel, beech, oak, and alder. The IgE cross-reactivity between Bet v 1 and homologous PR-10 proteins in plant foods such as fruits, vegetables and nuts is a key factor in the development of oral allergy syndrome (OAS).
Epidemiology
In Europe the prevalence of birch pollen sensitization ranges from approximately 8% to 16% in the general population.
Regarding Bet v 1 sensitization in the European general population, a study of 501 adolescents in Austria found that 16.3% of participants had IgE-reactivity to Bet v 1. Similarly, a German study of 17,641 children and adolescents reported that 14.1% were sensitized to Bet v 1.
Among European patients with tree-pollen allergy, a retrospective study of 854 patients with birch pollen sensitization in Italy, reported that sensitization to Bet v 1 ranged from 53% to 95%, depending on the region. In a study of 260 patients with tree pollen allergy in Germany, 239 (92%) patients were sensitized to Bet v 1. Of these 239 patients, all (100%) also showed IgE-reactivity to hazel and alder pollen extract.
A study from Japan detected specific IgE towards Bet v 1 in 39 (97,5%) out of 40 patients' sera with specific IgE towards birch pollen extract and in a study from Korea involving 31 children with specific IgE to birch pollen, 24 children (77%) were sensitized to Bet v 1. Among the Korean children, 13 had oral allergy syndrome (OAS), and all of them (100%) were Bet v 1 sensitized. Bet v 1 sensitization was detected in 11 (61%) out of 18 children without OAS.
A study from Beijing, China involving 58 birch pollen allergic patients detected Bet v 1 sensitization in 48 (82.8%) patients. Similarly, in a study conducted in northern China, 203 patients with allergic rhinitis or asthma were tested for specific IgE against birch pollen extract and Bet v 1. Among the 203 patients, 16.7% (n=34) had specific IgE to birch pollen extract, and of those, 82.4% (n=28) had specific IgE to Bet v 1. This study also found that most patients sensitized to Bet v 1 showed IgE-reactivity to the apple allergen Mal d 1 and the soybean allergen Gly m 4, potentially leading to manifestations of oral allergy syndrome.
The prevalence of birch pollen sensitization in the United States is reported to be approximately 7% among individuals aged 6 years and older. However, there is a paucity of published data regarding the prevalence of Bet v 1 sensitization in North America.
Route Of Exposure
The main exposure route for Bet v 1 is through inhalation (airway) of birch pollen as Bet v 1 is released from pollen on the mucosa.
Exposure to Bet v 1 homologous PR-10 proteins can occur via ingestion of certain fruits, vegetables and nuts causing symptoms of oral allergy syndrome (OAS).
Clinical Relevance
Bet v 1 is a primary sensitizer in birch pollen-endemic regions, leading to allergic reactions such as allergic rhinoconjunctivitis with typical symptoms sneezing, runny or blocked nose, itchy and watery eyes, and general nasal congestion. In Bet v 1 sensitized individuals, exposure to birch pollen can lead to asthmatic symptoms, including wheezing, shortness of breath, chest tightness, and coughing.
Sensitization to Bet v 1 can lead to IgE-mediated cross-reactivity to homologous allergens present in various fruits, vegetables, and nuts, potentially causing oral allergy syndrome (OAS). Symptoms of OAS typically include itching, tingling, and swelling in the mouth and throat. A study from Korea found that 20% (n=25) of birch pollen sensitized patients developed OAS. Among these patients suffering from OAS, symptoms included rhino-conjunctivitis (75%), asthma (20%), and chronic urticaria (12%). Although rare, some individuals may experience more severe systemic reactions.
Diagnostics
Bet v 1 has been recommended as a marker allergen to identify patients with genuine sensitization to birch pollen and Bet v 1 sensitization is considered important for the selection of patients suitable for birch pollen AIT. Studies on cross-reactivity have shown that patients with specific IgE to Bet v 1 are also IgE-reactive to Bet v 1 homologous allergens from the order Fagales (hazel, alder, hornbeam, oak), and from certain plant-based foods indicative of OAS manifestations. Specific IgE cut-off levels in kUA/L have been proposed for identifying OAS patients but these varies between populations and region.
Prevention And Therapy
Bet v 1 sensitization is considered important for the selection of patients suitable for birch pollen allergen specific immunotherapy (AIT).
Experimental AIT trials
In a 2-year randomized placebo-controlled trial involving 134 subjects, subcutaneous AIT using recombinant Bet v 1 demonstrated similar efficacy to conventional birch pollen extract AIT and AIT with Bet v 1 purified from pollen in reducing rhino-conjunctivitis symptoms and the use of rescue medication.
Subcutaneous AIT with a hypoallergenic recombinant Bet v 1 variant was compared to conventional birch pollen extract AIT in a recent 6-month trial involving 47 subjects. Despite skin prick test (SPT) confirmation of hypo-allergenicity (approximately 50% compared to natural Bet v 1), more adverse events were reported in response to the hypoallergenic Bet v 1 AIT than with the conventional extract AIT.
In a sublingual AIT multicentre, placebo-controlled study conducted in 483 patients with birch pollen-induced rhinoconjunctivitis, recombinant Bet v 1 AIT showed efficacy results consistent with what is observed following sublingual AIT with birch pollen extract.
Cross-Reactivity
There is a high degree of amino acid sequence identity between Bet v 1 and its homologous allergens in Fagales pollen, with Car b 1 (hornbeam), Aln g 1 (alder), and Cor a 1 (hazel) showing 79% to 83% identity. Que a 1 (oak) has a 58% amino acid sequence identity with Bet v 1. The major allergens of chestnut (Cas s 1) and beech (Fag s 1) display 75% and 69% (N-terminal) amino acid sequence homology with Bet v 1, respectively. This high degree of sequence identity leads to similar tertiary structures, and the molecular structure of Bet v 1 has revealed conformational epitopes involved in IgE cross-reactivity.
Similarly, the amino acid sequence similarities between Bet v 1 and PR-10 proteins in certain fruits, nuts, and vegetables can be high, such as approximately 60% between Bet v 1 and the apple allergen Mal d 1. This leads to similar three-dimensional structures and potential IgE cross-reactivity. The extent of cross-reactivity in an individual patient is determined by the degree of sequence and structural similarities, as well as the epitope repertoire of Bet v 1 IgE antibodies.
Foods containing Bet v 1 homologous PR-10 protein includes apple, pear, cherry, peach, nectarine, apricot, plum, kiwi, carrot, celery, hazelnut, almond, walnut and soybean.
Explained Results
Allergen information
Bet v 1 belongs to the PR-10 protein family and is the major allergen of birch pollen. Sensitization to Bet v 1 has been reported in up to 95% of individuals allergic to birch pollen. Bet v 1 is heat labile allergen. There are nearly 30 isoforms of Bet v 1 described. Bet v 1 homologous PR-10 proteins are found in other Fagales tree pollens, as well as in various fruits, nuts and vegetables.
Clinical relevance
Bet v 1 is a primary sensitizer in birch pollen-endemic regions, leading to allergic rhinitis and sometimes asthma. Sensitization to Bet v 1 can lead to food oral allergy syndrome (OAS).
Cross-reactivity
There is extensive IgE cross-reactivity between Bet v 1 and pollen allergens from other Fagales trees such as hazel, beech, oak, and alder, and to homologous allergenic PR-10 proteins in plant foods such as fruits, vegetables and nuts.
References
- Author: Turacoz Healthcare Solutions
- Reviewer: Dr. Magnus Borres
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