Brazil nut

  • Allergen search puff

    SEARCH FOR ALLERGENS

    Search ImmunoCAP allergens and allergen components. Note that all information is in English.

Code: f18
Latin name: Bertholletia excelsa
Source material: Shelled nuts
Family: Lecythidaceae
Common names: Brazil nut, Para-nut, Cream nut

Allergen Exposure

Geographical distribution
The Brazil nut is actually the seed of a giant tree that grows wild in South America's Amazon jungle. The seeds, about 6 cm long, come in clusters of 8 to 25 inside a large, hard, thick-walled globular pod that resembles a Coconut and weighs up to 2 kg. The extremely hard shell of each seed is dark-brown and 3-sided. The kernel is white and high in oil, containing about 70% oil and 17% protein. When fresh it is highly esteemed for its rich flavour, but it becomes rancid in a short time from the great quantity of oil it contains. Except for its close relative the Paradise nut, it is not closely related to any other food.

Brazil nut exportation from the Amazon was begun in the 1600s by Dutch and Portuguese traders. The monetary value of the nuts (nearly all from wild trees) is second only to that of rubber.

Environment
In the Amazon, indigenous tribes eat the nuts raw, or grate them and mix them into gruels, often along with Manioc flour. The plentiful oil is used in cooking. Exported, the nuts are a snack food, and their oil is prized. In addition to protein and fat, Brazil nuts are a substantial source of selenium, an important antioxidant. The proteins, though making up only 15-17% of the nuts' fresh weight, comprise 50% of the defatted flour. Storage proteins are the most important ones, and the 12S globulin legumin-like protein and the 2S albumin have been identified as the most representative. The 2S protein is high in sulfur-rich amino acid (3-8% cysteine and 18% methionine) (1). The proteins are also extremely rich in glutamine, glutamic acid, and arginine.

The tree bark is brewed into tea to treat liver ailments. The husks of the seed pods have also been brewed to treat stomach aches.

Unexpected exposure
Brazil nut may be a "hidden" allergen in cookies, etc. The oil extracted from the nuts is commonly used in Peru and other South American countries to manufacture soap, and for lighting, and the empty pods are used as implements and burned to repel insects. Worldwide, Brazil nut oil is often used in soaps, shampoos, hair conditioning/repair products, and skin moisturisers, and extracts of the pods can figure in insect repellents.

Allergens
A number of allergenic proteins has been isolated from Brazil nut. These range in size from 4 kDa to 58 kDa. In a study of a group of patients with IgE antibodies to Brazil nut, comprising 11 patients with anaphylaxis to eating Brazil nuts and 10 asymptomatic subjects, sera from all the symptomatic patients recognised a 9 kDa allergen corresponding to 2S albumin of Brazil nut, whereas the other allergens each bound IgE antibodies from less than 50% of sera. No IgE binding to the 9 kDa allergen occurred in sera from asymptomatic subjects, but allergenic proteins of 25 to 58 kDa were recognised and were identified as minor allergens (5). Other minor allergens have been detected: of 18, 25, 33, and 45 kDa (2), including a 12S globulin protein, which is a legumin-like storage globulin (1).

The allergens characterised to date are:

  • Ber e 1, a 9 kDa protein, a 2S albumin, resistant to digestion by pepsin, and a major allergen (3-14).
     
  • Ber e 2, an 11S globulin-like protein (10,13,15).

The main immunoglobulin E epitope region of the 2S albumin, Ber e 1, is very stable to gastric digestion (3,8,16).

The Brazil nut 2S albumin has been recognised as a methionine-rich protein that could be used to increase the nutritional value of certain foods through genetic engineering techniques. However, the 2S albumin of the Brazil nut is also the major allergen of Brazil nuts (Ber e 1) and shows IgE-reactivity with more than 80% of the sera from Brazil nut-allergic subjects. This was demonstrated in transgenic Soybean: the newly expressed protein retained its allergenicity (17-18).

Potential cross-reactivity

An extensive cross-reactivity within the family can be expected (19).

Brazil nut contains a 2S albumin storage protein, a protein common to many seeds, which displays similarity to the 2S albumin of Cotton, Cocoa bean, Sunflower seed, Rape seed, Castor bean, English walnut (Jug r 1), Mustard seed (Sin a 1) and Sesame seed (Ses i 2). Comparison of the amino acid sequence shows high sequence similarity, from 34% between Sunflower seed and Brazil nut, to >52% similarity and >38% identity between Brazil nut and many other plant 2S albumins (20-24). The English walnut allergen (Jug r 1) exhibits a 46.1% identity with the Brazil nut 2S albumin seed storage protein, Ber e 1 (24-25).

The 2S albumins have been shown to play a significant role in cross-reactivity between Walnut Jug r 1 and Pecan nut Car i 1, as a result of the high degree of structural homology of the 2S albumins in these 2 tree nuts. However, a study of the con-formational analysis of the linear IgE-binding epitopes mapped on the molecular surface of Ara h 2, a 2S albumin, showed no structural homology with the corresponding region of Brazil nut Ber e 1; this indicates that allergenic cross-reactivity observed between Peanut and Brazil nut may depend on other ubiquitous seed storage protein allergens, e.g., the vicilins (26).

However, a recent study evaluating cloned Peanut Ara h 2 reported that when serum from Peanut-allergic patients is pre-incubated with increasing concentrations of Almond or Brazil nut extract, IgE binding to rAra h 2 is inhibited. Purified rAra h 2-specific serum IgE antibodies also bound to proteins present in Almond and Brazil nut extracts through immunoblotting, which indicates that the Peanut allergen Ara h 2 shares IgE-binding epitopes with both Almond and Brazil nut allergens (27). The same authors had previously reported that Peanut-specific antibodies from sera of Peanut-allergic subjects became activated following stimulation with Peanut, Almond and Brazil nut extracts, demonstrating biological activity of cross-reactive IgE antibodies (28).

 A 2S albumin has been isolated from the seed of Tomato and was found to cross-react with antiserum to the fruit lectin. The sequence of the fruit lectin was shown to be similar to that of 2S albumins from different plants, such as Brazil nut and Castor beans (29). The allergenicity of the Tomato seed 2S albumin was not evaluated.

Walnut-induced anaphylaxis has been reported, with cross-reactivity to Hazel nut and Brazil nut described (30).

Clinical Experience

IgE-mediated reactions
Allergy to Brazil nut is common, frequently has an onset in the first few years of life, generally persists, and accounts for severe and potentially fatal allergic reactions. The ubiquity of this food in the modern diet makes avoidance difficult, and accidental ingestions, with reactions, are common (1,31-36). Symptoms include vomiting, diarrhoea and other manifestations associated with food allergy: laryngeal oedema, atopic dermatitis, urticaria and anaphylaxis (1, 36-37).

The probability of patients with nut allergy having IgE antibodies to a particular combination of Peanut, Hazel nut and Brazil nut is similar, whatever the patients' age or sex. The apparent increase in multiple nut reactivity with increasing age may therefore be due to exposure of previously unchallenged sensitivity. The frequency of multiple-nut specificity is sufficiently high that patients should always be tested for allergy to a range of nuts if they have a history of reacting to any nut (38). In a study of 62 patients (adults and children) with nut allergy, Peanuts were the commonest cause of allergy (n=47), followed by Brazil nut (n=18), Almond (n=14), and Hazel nut (n=13) (35).

In an American study of 115 patients aged 4-19.5 years, 2% (n=1) were graded as mildly allergic to Brazil nut, and 4% (n=2) were graded as severely allergic. The study also concluded that around 9% of children with tree nut allergy outgrow their allergy. (39) An earlier American study by the Food Allergy and Anaphylaxis Network (FAAN) Peanut and Tree Nut Allergy Registry collected information on 5,149 patients (mainly children) and found that 34% were allergic to Walnut, followed by Cashew (20%), Almond (15%), Pecan (9%), and Pistachio (7%). Less than 5% each were allergic to Hazel, Brazil, Pine, Macadamia and Hickory nuts (40). It is evident that the frequency of reported allergy depends on the population group being studied and that in countries where the consumption of Brazil nut is low, the prevalence of reported allergy to this nut will be low.

A study reports on 11 patients with anaphylaxis after eating Brazil nuts and on 10 subjects with no symptoms to this food, although both groups had IgE antibodies to Brazil nut. A number of allergenic components with molecular weights ranging from 4 to 58 kDa were isolated. All sera from symptomatic patients recognised the Brazil nut 2S albumin, whereas the other allergens each bound IgE antibodies from less than 50% of sera. No sera from asymptomatic subjects showed IgE antibody binding to the 2S albumin, but sera did recognise 25 to 58 kDa components, which are minor allergens (5). Therefore, minor Brazil nut allergens were thought to result only in sensitisation to Brazil nut and not in allergic symptoms (5). However, this is contradicted by a study of a 15-year-old boy who experienced 2 distinct episodes of generalised urticaria about 30 minutes after eating Brazil nut. An IgE antibody test was very positive to Brazil nut. Serum IgE was positive to Brazil nut but negative to Mustard, Poppy seed, Sesame seed and Sunflower seed, suggesting no sensitisation to the 2S albumin allergen (2). The 2S albumins may be very important in food-induced anaphylaxis (6).

Anaphylaxis to Brazil nut has been reported. A British report from the Isle of Wight (population 125,000) described 12 cases of allergy to Brazil nut recorded over 8 years from 1983 to 1991. Eleven patients developed angioedema, 7 generalised urticaria, 5 bronchospasm, 2 stridor, 2 throat tightness, 2 itchy mouth and 1 syncope. Onset of symptoms was less than 1-3 minutes in all. Eight patients were shown to have significant skin reactivity for Brazil nut. In 6 out of 8 patients, Brazil nut IgE antobodies were demonstrated (> 0.7 kUA/l). In 3 patients there was no definite evidence of IgE-mediated hypersensitivity. Total IgE was normal in 5 patients with severe reactions. Ten out of 12 patients had other atopic diseases such as asthma, eczema or allergic rhinitis, usually from infancy or early childhood. Seven out of 8 patients were positive to several food and/or inhalant allergens on skin test (36).

Anaphylaxis to Brazil nut may occur even with no previous history of ingestion of this nut. This was reported from SPT investigation for Brazil nut sensitisation in a young adult who had experienced an adverse reaction presumed to be a result of allergy to Walnut. Immediately after the skin was pricked with fresh Brazil nut, an episode of severe anaphylaxis occurred, requiring epinephrine and intravenous steroids. The authors thought this might have resulted from cross-reactivity, as occurs with other tree nuts (41).

Anaphylaxis was also reported in a 31-year-old woman, known to have rhinoconjunctivitis and asthma, who developed pharyngeal itching, lip swelling, dysphonia, dyspnoea, wheezing, and generalised macular exanthema 10 minutes after eating a Brazil nut. She had previously developed oral allergy syndrome after eating Almond, Walnut, Sunflower seed, and Hazel nut. She had suffered from abdominal pain after eating Chestnut. She tolerated Peanut and Pistachio. Skin reactivity was detected for Brazil nut, Almond, Peanut, Chestnut, Sunflower seed, Pistachio, Hazel nut, Walnut, and Cashew nut. Serum IgE was raised for Almond, Peanut, Chestnut, Pistachio, Hazel nut and Sunflower seed. IgE antibody level to Brazil nut was 2.37 kUA/l (37).

Patients sensitised to minor Brazil nut allergens are reported to not have allergic symptoms (5), but this is contradicted by a report on a 15-year-old boy who experienced 2 distinct episodes of generalised urticaria about 30 minutes after eating Brazil nut. SPT and serum IgE was present for Brazil nut. As serum IgE was present for Brazil nut but not for Mustard, Poppy seed, Sesame seed or Sunflower seed, the authors concluded that no reactivity was therefore shown to 2S albumins, which suggests that a minor allergen was involved (2).

Food allergens have been reported to be present in breast milk. A study also reports on a 20-year-old woman with documented Brazil nut allergy who developed widespread urticaria and mild dyspnoea after intercourse with her boyfriend, who had earlier consumed Brazil nuts. SPT evaluation with the boyfriend's semen after Brazil nut consumption confirmed significant reactivity, whereas a sample before nut consumption was negative (42).

In a study to find the best approach to the diagnosis of Brazil nut allergy, 56 children and adults with a history of an allergic reaction to Brazil nut or other evidence of sensitisation were evaluated by questionnaire, SPT and serum IgE antibodies to Brazil nut, and by double-blind, placebo-controlled labial and, if necessary, oral challenges. The study concluded that a combination of history, SPT and IgE antibodies was adequate for achieving a diagnosis in the approximately 77% of patients with suspected Brazil nut allergy. However, a doubtful history combined with SPT result (between 1 and 5 mm), or a IgE antibody level less than 3.5 kUA/l, may require an oral challenge to help determine the risk of a Brazil nut allergic reaction (43).


Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

  1. Bartolome B, Mendez JD, Armentia A, Vallverdu A, Palacios R. Allergens from Brazil nut: immunochemical characterization. Allergol Immunopathol (Madr) 1997;25(3):135-44
  2. Asero R, Mistrello G, Roncarolo D, Amato S. Allergy to minor allergens of Brazil nut. Allergy 2002;57(11):1080-1
  3. Murtagh GJ, Dumoulin M, Archer DB,
    Alcocer MJ. Stability of recombinant 2 S albumin allergens in vitro.
    Biochem Soc Trans 2001;30(6):913-5
  4. Alcocer MJ, Murtagh GJ, Bailey K, Dumoulin M, Meseguer AS, Parker MJ, Archer DB. The disulphide mapping, folding and characterisation of recombinant Ber e 1, an allergenic protein, and SFA8, two sulphur-rich 2S plant albumins.
    J Mol Biol 2002;324(1):165-75
  5. Pastorello EA, Farioli L, Pravettoni V, Ispano M, Conti A, Ansaloni R, Rotondo F, Incorvaia C, Bengtsson A, Rivolta F, Trambaioli C, Previdi M, Ortolani C. Sensitization to the major allergen of Brazil nut is correlated with the clinical expression of allergy. J Allergy Clin Immunol 1998;102(6 Pt 1):1021-7
  6. Pastorello EA, Pompei C, Pravettoni V, Brenna O, Farioli L, Trambaioli C, Conti A. Lipid transfer proteins and 2S albumins as allergens. Allergy 2001;56 Suppl 67:45-7
  7. Alcocer MJ, Murtagh GJ, Wilson PB, Progias P, Lin J, Archer DB. The major human structural IgE epitope of the Brazil nut allergen Ber e 1: a chimaeric and protein microarray approach. J Mol Biol 2004;343(3):759-69
  8. Moreno FJ, Mellon FA, Wickham MS, Bottrill AR, Mills EN. Stability of the major allergen Brazil nut 2S albumin (Ber e 1) to physiologically relevant in vitro gastrointestinal digestion.
    FEBS J 2005;272(2):341-52
  9. Koppelman SJ, Nieuwenhuizen WF, Gaspari M, Knippels LM, Penninks AH, Knol EF, Hefle SL, de Jongh HH. Reversible denaturation of Brazil Nut 2S albumin (Ber e1) and implication of structural destabilization on digestion by pepsin.
    J Agric Food Chem 2005; 53(1):123-31
  10. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/List.htm 2007
  11. Moreno FJ, Rubio LA, Olano A, Clemente A. Uptake of 2S albumin allergens, Ber e 1 and Ses i 1, across human intestinal epithelial Caco-2 cell monolayers.
    J Agric Food Chem 2006;54(22):8631-9
  12. Tengel T, Alcocer MJ, Schleucher J, Larsson G. Complete Assignment and Secondary Structure of the Brazil Nut Allergen Ber e 1. J Biomol NMR 2005;32(4):336
  13. Roux KH, Teuber SS, Sathe SK. Tree nut allergens. Int Arch Allergy Immunol 2003;131(4):234-44
  14. Gander ES, Holmstroem KO, De Paiva GR, De Castro LA, Carneiro M, et al. Isolation, characterization and expression of a gene coding for a 2S albumin from Bertholletia excelsa (Brazil nut). Plant Mol Biol 1991;16(3):437-48
  15. Guo F, Jin T, Howard A, Zhang YZ. Purification, crystallization and initial crystallographic characterization of brazil-nut allergen Ber e 2. Acta Crystallogr Sect F Struct Biol Cryst Commun 2007;63(Pt 11):976-9.
  16. Murtagh GJ, Archer DB, Dumoulin M, Ridout S, Matthews S, Arshad SH, Alcocer MJ. In vitro stability and immunoreactivity of the native and recombinant plant food 2S albumins Ber e 1 and SFA-8.
    Clin Exp Allergy 2003;33(8):1147-52
  17. Nordlee JA, Taylor SL, Townsend JA, Thomas LA, Bush RK. Identification of a Brazil-nut allergen in transgenic soybeans.
    N Engl J Med 1996;334(11):688-92
  18. Oommen A, Kelly J, Benson A, Hefle S Identification of IgE-binding epitopes of the Brazil nut 2S albumin allergen. AAAAI 56th Annual Meeting 2000;March 3-8
  19. Yman L. Botanical relations and immuno-logical cross-reactions in pollen allergy. 2nd ed. Pharmacia Diagnostics AB. Uppsala. Sweden. 1982: ISBN 91-970475-09
  20. Kochhar S, Gartenmann K, Guilloteau M, McCarthy J. Isolation and characterization of 2S cocoa seed albumin storage polypeptide and the corresponding cDNA.
    J Agric Food Chem 2001;49(9):4470-7
  21. Kelly JD, Hlywka JJ, Hefle SL. Identification of sunflower seed IgE-binding proteins. Int Arch Allergy Immunol 2000;121(1):19-24
  22. Kortt AA, Caldwell JB, Lilley GG, Higgins TJ. Amino acid and cDNA sequences of a methionine-rich 2S protein from sunflower seed (Helianthus annuus L.).
    Eur J Biochem 1991;195(2):329-34
  23. Menendez-Arias L, Moneo I, Dominguez J, Rodriguez R. Primary structure of the major allergen of yellow mustard (Sinapis alba L.) seed, Sin a I.
    Eur J Biochem 1988;177(1):159-66
  24. Teuber SS, Dandekar AM, Peterson WR, Sellers CL. Cloning and sequencing of a gene encoding a 2S albumin seed storage protein precursor from English walnut (Juglans regia), a major food allergen. J Allergy Clin Immunol 1998 Jun;101(6 Pt 1):807-14
  25. Beyer K, Bardina L, Grishina G, Sampson HA. Identification of sesame seed allergens by 2-dimensional proteomics and Edman sequencing: seed storage proteins as common food allergens.
    J Allergy Clin Immunol 2002;110(1):154-9
  26. Barre A, Borges JP, Culerrier R, Rouge P. Homology modelling of the major peanut allergen Ara h 2 and surface mapping of IgE-binding epitopes.
    Immunol Lett 2005;100(2):153-8
  27. de Leon MP, Drew AC, Glaspole IN, Suphioglu C, O'Hehir RE, Rolland JM. IgE cross-reactivity between the major peanut allergen Ara h 2 and tree nut allergens.
    Mol Immunol 2007;44(4):463-71
  28. de Leon MP, Drew AC, Glaspole IN, Suphioglu C, Rolland JM, O'Hehir RE. Functional analysis of cross-reactive immunoglobulin E antibodies: peanut-specific immunoglobulin E sensitizes basophils to tree nut allergens.
    Clin Exp Allergy 2005;35(8):1056-64
  29. Oguri S, Kamoshida M, Nagata Y, Momonoki YS, Kamimura H. Characterization and sequence of tomato 2S seed albumin: a storage protein with sequence similarities to the fruit lectin. Planta 2003;216(6):976-84
  30. Asero R, Mistrello G, Roncarolo D, Amato S. Walnut-induced anaphylaxis with cross-reactivity to hazelnut and Brazil nut.
    J Allergy Clin Immunol 2004;113(2):358-60
  31. Sicherer SH, Sampson HA. Peanut and tree nut allergy.
    Curr Opin Pediatr 2000;12(6):567-73
  32. Hide DW. Clinical curio: allergy to Brazil nut. Br Med J (Clin Res Ed) 1983;287(6396):900
  33. Gillespie DN, Nakajima S, Gleich GJ. Detection of allergy to nuts by the radioallergosorbent test.
    J Allergy Clin Immunol 1976;57(4):302-9
  34. Dutau G, Rittie JL, Rance F, Juchet A, Bremont F. New food allergies. [French] Presse Med 1999;28(28):1553-9
  35. Ewan PW. Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations.
    BMJ 1996;312(7038):1074-8
  36. Arshad SH, Malmberg E, Krapf K, Hide DW. Clinical and immunological characteristics of Brazil nut allergy.
    Clin Exp Allergy 1991;21(3):373-6
  37. Borja JM, Bartolome B, Gomez E, Galindo PA, Feo F. Anaphylaxis from Brazil nut.
    Allergy 1999;54(9):1007-8
  38. Pumphrey RS, Wilson PB, Faragher EB, Edwards SR. Specific immunoglobulin E to peanut, hazelnut and brazil nut in 731 patients: similar patterns found at all ages. Clin Exp Allergy 1999;29(9):1256-9
  39. Fleischer DM, Conover-Walker MK, Matsui EC, Wood RA. The natural history of tree nut allergy. J Allergy Clin Immunol 2005;116(5):5-1093
  40. Sicherer SH, Furlong TJ, Munoz-Furlong A, Burks AW, Sampson HA. A voluntary registry for peanut and tree nut allergy: characteristics of the first 5149 registrants.
    J Allergy Clin Immunol 2001;108(1):128-32
  41. Senna G, Bonadonna P, Crivellaro M, Schiappoli M, Passalacqua G. Anaphylaxis due to Brazil nut skin testing in a walnut-allergic subject. J Investig Allergol Clin Immunol 2005;15(3):225-7
  42. Bansal AS, Chee R, Nagendran V, Warner A, Hayman G. Dangerous liaison: sexually transmitted allergic reaction to Brazil nuts.
    J Investig Allergol Clin Immunol 2007;17(3):189-91
  43. Ridout S, Matthews S, Gant C, Twiselton R, Dean T, Arshad SH. The diagnosis of Brazil nut allergy using history, skin prick tests, serum-specific immunoglobulin E and food challenges.
    Clin Exp Allergy 2006;36(2):226-32

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.