Ber e 1
Summary
Ber e 1 is a 9-kDa, 2S albumin recognized as the major allergen of Brazil nut, that is resistant to both, heat as well as pepsin digestion. This allergen belongs to the prolamin superfamily of proteins. The prevalence of allergy to Brazil nut has frequently been found in the United States and United Kingdom (UK), with specific immunoglobulin E reactivity to Ber e 1 commonly reported in individuals living in the UK. Interestingly, Ber e 1 has been considered as the first food allergen that may pass on from one plant to the other via genetic engineering technology. Furthermore, patients sensitive to Ber e 1 allergen may develop severe reactions, such as urticaria, laryngeal edema, or even anaphylactic shock. Ber e 1 has displayed sequence identity with 2S albumins from cocoa, upland cotton and English walnut; whereas sequence similarity with 2S albumins from pumpkin, arabdopsis, mabinlin, and rapeseed. Additionally, sequence identity and structural homology has also been found with 2S albumins of sesame and sunflower.
Epidemiology
Worldwide distribution
Allergy to Brazil nuts (Bertholletia excelsa) is frequently been reported in the United Kingdom (UK) as well as in the United States (US). A systematic review involving 36 studies reported the prevalence of Brazil nut allergy to be between 24% and 33% in the UK and between 12% and 22% in the US, among tree-nut-allergic individuals.
A study was conducted in Italy on 11 symptomatic Brazil nut-allergic patients (severe anaphylaxis due to consumption of Brazil nut) and 10 asymptomatic patients (no clinical symptoms, but having positive immunoglobulin E (IgE) reactivity to Brazil nut). It was found that 100% of symptomatic patients showed IgE reactivity to Ber e 1, while none of the asymptomatic patients were positive for specific IgE (sIgE) to Ber e 1.
In a study conducted on 56 patients who were evaluated for Brazil nut allergy, sIgE to recombinant (r) Ber e 1 was measured in 36 patients, among which 16 were found to be positive (44.4%). Besides, another study conducted in UK among 18 patients with Brazil nut allergy, sIgE reactivity to Ber e 1 was reported in 94.4% of patients (17 out of 18).
Interestingly, Ber e 1 is a protein rich in sulfur, containing amino acids like methionine (18% of total protein) and cysteine (8%). This property of 2S albumin of Brazil nut has made it as a potential candidate in increasing the nutritional value of certain foods (tobacco, rapeseed, beans) and legumes (soybean and Vicia narbonensis) via genetic engineering technology. However, since Brazil nut is also reported to be allergic, the genetically-modified foods with Ber e 1 could present with allergic reactions, and hence should be considered for its safety. In line with this, a study evaluated the IgE reactivity to Ber e 1 (both Brazil nut 2S albumin and transgenic 2S albumin in soybean) in 9 Brazil nut-allergic patients. The Ber e 1-sIgE was found to be positive in 88.9% (8 out of 9) of these individuals. Also, 77.8% (7 out of 9) of Brazil nut-allergic patients showed IgE reactivity towards transgenic soybean protein, similar to 2S albumin of Brazil nut. In addition, it was found that this protein was not present in the non-transgenic extract of soybean. Thus, Ber e 1 could be considered as the first food allergen that may pass on from one plant to the other.
Clinical Relevance
Disease Severity
Ber e 1 is reported to be the major allergen of Brazil nut and found to be associated with the clinical expression of Brazil nut allergy in sensitized individuals. Furthermore, the IgE reactivity to 2S albumin of Brazil nut i.e. Ber e 1 has been reported to be correlated with the food-induced-anaphylaxis. In a study conducted on 11 symptomatic patients manifesting anaphylaxis (urticaria, laryngeal edema, or anaphylactic shock) on ingestion of Brazil nuts, Ber e 1 was recognized by the sera of all the patients (100%). In the same study, 10 non-symptomatic Brazil nut-sIgE sensitized individuals were studied, who were found negative for Ber e 1-sIgE.
Further, another study was conducted on a cohort of 36 patients with suspected allergy to Brazil nut. The patients were considered as true positive, if they reacted positive on oral challenge or skin prick test with a history of Brazil nut allergy, whereas the patients were considered as true negative if the oral challenge was negative or presented with a history of clinical non-reactivity. The sIgE reactivity to Ber e 1 was reported in 15 true positive patients, while it was found only in one true negative patient.
A recent study has postulated that naturally-existing plant lipids may play an essential role in the inherent allergenicity of Ber e 1.
Diagnostics
Disease Severity
Ber e 1 has been found to be the only allergen in Brazil nut, associated with clinical manifestations of its allergy. A study was conducted on 11 patients with positive IgE and clinical symptoms to Brazil nut (symptomatic) and 10 patients with only positive IgE but no clinical symptoms (non-symptomatic). The results revealed that only the 11 symptomatic patients were positive for sIgE to Ber e 1, while none of the 10 non-symptomatic patients showed IgE reactivity to Ber e 1. This suggests that sensitization to Ber e 1 is associated with the development of clinical allergy to Brazil nut.
Furthermore, it was found that sIgE-Ber e 1 could help differentiate patients with a true allergy to Brazil nuts, from the patients who showed only sensitization and no clinical symptoms towards Brazil nut ingestion.
Exposure
The main route of exposure is through ingestion.
Cross-Reactivity
Several 2S albumins from different sources have shown sequence similarity and/or identity among them. Ber e 1 was reported to be 36%, 39% and 44% identical to 2S albumins from cocoa (Theobroma cacao), upland cotton (Gossypium hirsutum) and English walnut (Juglans regia), respectively. Furthermore, the sequence similarity of 53%, 50%, 42%, 40% and >52% was observed with 2S albumins of pumpkin (Cucurbita maxima), arabdopsis (Arabidopsis thaliana), mabinlin (Capparis masaikai), rapeseed (Brassica napus), and cocoa, respectively.
The structural homology between Ses i 2 (2S albumin from sesame seeds) and Ber e 1 was reported to be 40%. Moreover, the other 2S albumin from sesame i.e. Ses i 1 was reported to have some degree of amino-acid sequence homology with Ber e 1. Furthermore, sequence homology between 2S albumin of sunflower and Ber e 1 was found to be 34%.
Common epitopes for IgE binding have been reported from Ber e 1 and other 2S albumins, like yellow mustard (Sin a 1), oriental mustard (Bra j 1) as well as English walnut (Jug r 1).
References
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