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Whole Allergen

f18 Brazil nut

f18 Brazil nut Scientific Information

Type:

Whole Allergen

Display Name:

Brazil nut

Route of Exposure:

Ingestion

Family:

Lecythidaceae

Species:

Bertholletia excelsa

Latin Name:

Bertholletia excelsa

Other Names:

Brazil nut, Para-nut, Cream nut

Related Allergens: f354 Ber e 1

Summary

Bertholletia excelsa, also known as Brazil nut, is an important tree belonging to the family of Lecythidaceae, that has high socio-economic value. It is considered as an indigenous tree to the Amazon tropical rainforest, and its nuts are found to be the only internationally traded seeds that are gathered by forest-based harvesters. The prevalence of Brazil nut allergy has commonly been reported in the United Kingdom (24% and 33%) and United States (12% and 22%). Brazil nut allergy occurs primarily through oral ingestion. Furthermore, allergy to this nut may usually be associated with systemic reactions involving the respiratory tract, cardiovascular, neurological, gastrointestinal system or skin (urticaria or angioedema, and sometimes even life-threatening reactions, like anaphylaxis. Ber e 1 and Ber e 2 are the major allergens identified in Brazil nut, with Ber e 1 being resistant to heat as well as pepsin digestion. It has been reported that Ber e 1-sIgE could serve as a good diagnostic marker in identifying true Brazil nut allergy. Cross-reactivity has been identified with botanically related tree nuts, such as pecan, walnut, hazelnut and cashew, and to some degree with 2S albumins of other plant species, such as cocoa seed, cottonseed, sunflower, sesame seed, rapeseed and castor seed.

Epidemiology

Worldwide distribution

Allergy to Brazil nut is frequently been reported in the United Kingdom (UK), as well as in the United States (US) (12-14).

A systematic review involving 36 studies conducted among tree-nut-allergic individuals, reported the prevalence of Brazil nut allergy to be between 24% and 33% in the UK and between 12% and 22% in the US (15).

An increasing trend in the prevalence of Brazil nut allergy was reported in the US (6). A cross-sectional telephone survey conducted across the US reported the allergy to Brazil nut in 12.5% (8 out of 64) of tree-nut allergic individuals in 1999 (16), which was found to increase to ~28% (25 out of 89) in 2003 (17). However, this 11-year follow-up study in 2010 found the prevalence to reduce to 22.6% (19 out of 84) in tree-nut allergic individuals (18).

The Pronuts study was a multicenter, European study (London, Geneva, and Valencia) that reported the prevalence of Brazil nut allergy to be 8.2% (10 of 122) among nut-allergic individuals, with the maximum Brazil nut-allergic individuals found in London (10%, 5 out of 50). However, it was not considered to be an index nut, as it was consumed less often across all centers (19).

Moreover, a study was conducted to examine the cross-sensitization profiles of tree nuts in birch-endemic areas in Finland. The results reported that the prevalence of Brazil nut allergy in tree-nut-allergic subjects, with and without birch sensitization was found to be 18% and 8%, respectively (20).

Furthermore, in a retrospective study conducted in Taiwan, sensitization to Brazil nut was reported to be 8.3% (28 out of 333) among food-sensitized individuals. Furthermore, it was found to be among the least frequent nut-related sensitization (21). 

Risk factors

Literature data have speculated that allergy to Brazil nut may elicit fatal allergic reactions in sensitized individuals, having a definite atopic family history (4).

Environmental Characteristics

Worldwide distribution

Brazil nut is indigenous to South America, mainly growing in the rain forests of Amazon (Brazil). It is spread throughout Brazil, Bolivia, Columbia, Ecuador, Peru, and Venezuela (4, 6).

The Manaus region, located in the state of Amazonas, Brazil, is considered as one of the largest producers of Brazil nut in the world, with about 1.2 million trees (1). Furthermore, this nut is exported to various destinations (4), since it is widely consumed across the world (7).

Route of Exposure

Main

Allergy to Brazil nuts can result in severe reactions, primarily through oral ingestion (19, 22).

Secondary

Interestingly, a case of sexually-transmitted nut allergy has been reported in a woman who developed immediate allergic reactions (urticaria and angioedema) to Brazil nuts after vaginal intercourse with the partner (23).

Clinical Relevance

Allergy to Brazil nut may generally be associated with systemic reactions involving the respiratory tract, cardiovascular, neurological, gastrointestinal system or skin (urticaria or angioedema) (14, 19, 22), and sometimes even life-threatening reactions, like anaphylaxis (22, 24).

Systemic reactions and Anaphylaxis

In a retrospective study conducted among 24 allergic patients (age: 7 months to 56 years) with systemic reactions after skin prick tests to different allergens, three patients were suspected to have allergy to Brazil nut. The systemic reactions were classified into grades based on the clinical symptoms, where grades 1, 2 and 3 were mild reactions, grade 4 was moderate and grade 5 was severe reactions. It was reported that Grade 2 symptoms were observed in two of the patients suspected with Brazil nut allergy. Furthermore, skin reactions, even when exposed to trace amounts (food or minute quantity of inhaled allergen) was observed in one patient, while the other reported of only rhinitis (25).

Furthermore, in the Pronuts study, an oral food challenge with Brazil nut (n=7) showed the highest symptom severity score (3.1 ± 0.9), when compared to the other nuts (almond, peanut, macadamia, pistachio, walnut, hazelnut, pecan, cashew, pine nut and sesame). The allergic reactions associated with Brazil nut were gastrointestinal (86%), skin, upper and lower respiratory (57% each), and cardiovascular/neurological (14%) reactions (19).

Interestingly, in a European Anaphylaxis Registry that collected the data on 1970 children, reported a case of a 13-year-old patient who presented with symptoms, such as angioedema, decreased responsiveness, vomiting and dyspnea, within 10 mins of exposure to Brazil nuts (24).

Allergic rhinitis

The prevalence of allergic rhinitis was reported to be 42.86% in Brazil nut-sensitized patients (n=28), in a retrospective study conducted among 333 food-sensitized individuals in Taiwan (21).

A study conducted among 56 suspected Brazil nut-allergic patients, allergic rhinitis was reported to be 87.5% (49 out of 56)  (22).

Asthma

In a retrospective study conducted among 333 food-sensitized patients (aged 2 to 93 years) in Taiwan, the prevalence of asthma was reported to be 21.43% in Brazil nut-sensitized patients (n=28) (21).

In a study conducted on a cohort of 56 patients with suspected Brazil nut allergy, asthma was found to be prevalent in 71.4% (40 out of 56) of patients (22).

Atopic Dermatitis

A retrospective study conducted among 333 food-sensitized patients in Taiwan reported the prevalence of asthma to be 46.43% in Brazil nut-sensitized patients (n=28) (21).

In a cohort of 56 patients with suspected allergy to Brazil nut, atopic dermatitis or eczema was reported to be 75% (42 out of 56)  (22).

Prevention and Therapy

Prevention strategies

Avoidance

Allergies to tree nuts are commonly being observed, that may become severe in certain individuals, hence it is generally advised to avoid consumption of tree nuts or the food products containing them in these individuals. Furthermore, it has been suggested that food manufacturers should mention allergenic substances on the food label, which include tree nuts as well (including Brazil nuts) (14).             

Molecular Aspects

Allergenic molecules

To date, two allergenic molecules have been identified, characterized and published officially by the World Health Organization (WHO) and International Union of Immunological Societies’ (IUIS) Allergen Nomenclature Subcommittee for Brazil nut (14, 26). The table below provides detailed information on each of the allergenic protein identified by WHO/IUIS as of 25 January 2021:

Allergen Isoallergen Biochemical Name Molecular Weight (kDa) Allergenicity
Ber e 1 Ber e 1.0101 2S albumin 9
  • Major allergen (11, 22).
  • Resistance to heat and pepsin digestion (6).
  • 100% of Brazil nut-allergic patients with anaphylaxis showed binding on immunoblots (n=11) (27).
  • Lesser immunoreactivity compared to Ber e 2 (11).
Ber e 2 Ber e 2.0101 11S globulin-like protein 29
  • Major allergen (11).
  • Also referred to as excelsin (12).
  • Specific IgE-binding was observed in 44% of Brazil nut-sensitized patients via Western blotting (12 out of 27) (28). 
Allergen Isoallergen Biochemical Name Molecular Weight (kDa) Allergenicity

kDa: kilodaltons, IgE: Immunoglobulin E

According to the literature, it has been revealed that the phospholipids in Brazil nut oil could play an important role in the inherent property of Ber e 1 to elicit allergic reactions (29).

Biomarkers of severity

The allergen Ber e 1 has been found to be thermostable and hence, roasting at 100°C for 20 min was not able to alleviate the allergenicity of the molecule. Ber e 1 has also been found to resist pepsin digestion. Furthermore, it has been reported that even alkaline treatment of the allergen was shown to be ineffective in reducing the immunoreactivity (6).

Ber e 1-sIgE may serve as a good diagnostic marker in identifying true Brazil nut allergy as compared to sIgE to whole Brazil nut extract (12, 22).

Cross-reactivity

Several studies have demonstrated that individuals reactive to one tree nut may be sensitized to the other, and this may be due to the cross-reactivity among their pan-allergens or nut storage proteins (30).

A survey was conducted to determine the true cross-reactivity between different tree-nut antigens. The tree nuts were categorized into two groups of cross-reactive nuts – strong: walnut, pecan, and hazelnut and moderate: Brazil nut, hazelnut, cashew, pistachio, and almond. The immunological cross-reactivity has been reported between Brazil nut, hazelnut, cashew, pistachio, and almond (moderate cross-reactive group), which may be because they belong to the same subclass i.e. Rosidae. However, cross-reactivity has also been observed among the members of the two groups of cross-reactive nuts i.e. between pecan and Brazil nut and between walnut and Brazil nut (31).

Further, the Pronuts study in Europe found the percentage of co-existent nut allergies with Brazil nut to be 70% with walnut (7 out of 10), 40% each with hazelnut, cashew, macadamia, pecan (4 out of 10), 30% with sesame (3 out of 10), 20% each with pistachio and peanuts (2 out of 10) and 10% with pine nut (1 out of 10) among 10 Brazil-nut allergic patients (19).

Additionally, IgE-mediated cross-reactivity between Brazil nut and walnut and pecan has also been found (30). In a study, cross-reactivity patterns were identified by xMAP multiplex food allergen detection assay, that found Brazil nut exhibiting cross-reactivity with cashew, hazelnut, and walnut (10).

It has been speculated that peanut-allergic individuals may be allergic to Brazil nut too (4).

Furthermore, moderate degree of co-sensitization exists between Brazil nut and coconut. This was supported by a retrospective analysis study that showed 58% of co-sensitization between Brazil nut and coconut, which was found to be statistically significant (p<0.001) (32).

Structural identity and similarity have been proposed between the 2S albumins of several foods. It has been reported that the 2S albumin of cocoa seed was found to share 44% of identity and 69% of similarity with the 2S albumin of Brazil nut (33, 34). Furthermore, cross-reactivity as a result of structural homology may be present between the 2S albumin of Brazil nut (Ber e 1) and other plant species, such as cottonseed, sunflower, rapeseed, castor bean, and sesame (35). 

Compiled By

Author: Turacoz Healthcare Solutions

Reviewer: Dr. Fabio Iachetti

 

Last reviewed: February 2021

References
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