Latin name: Bertholletia excelsa
Source material: rBer e 1 is a CCD-free recombinant protein
Common names: 2S Albumin
Brazil nut allergen components
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. Brazil nut may be eaten raw or roasted, and 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.
Allergy to Brazil nut is common. It 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, common (1-7).
A number of allergenic proteins has been isolated from Brazil nut. These range in size from 4 kDa to 58 kDa (8). A 9 kDa allergen corresponding to 2S albumin of Brazil nut has been identified as a major allergen. A number of other minor allergens have been detected: of 18 kDa, 25 kDa, 33 kDa, 45 kDa and 58 kDa, including a 12S globulin protein, a legumin-like storage globulin (8-9).
The following allergens have been characterised:
- Ber e 1, a 9 kDa protein, a 2S albumin, resistant to digestion by pepsin, and a major allergen (10-12).
- Ber e 2, an 11S globulin-like protein (13).
Allergens from Bertholletia excelsa listed by IUIS*
*International Union of Immunological Societies (www.allergen.org) Jan. 2008.
An E. coli strain carrying a cloned cDNA-encoding Bertholletia excelsa allergen, Ber e 1
Common names: 2S Albumin
Biological function: rBer e 1 is a 2S Albumin storage protein
Mw: 9 kDa
Ber e 1 is a 2S albumin, a common major storage protein found in a number of edible seeds and nuts and recognised as a panallergen. The 2S albumins are the major storage proteins in Walnut, Mustard, Sesame, Brazil nut, Peanut, Cottonseed, Sunflower and Castor bean (12,15-16).
Typical 2S albumins are small globular proteins that undergo proteolytic processing in the vacuoles of the plant cells, the full-length precursor protein is usually cloven into large and small subunits that stay associated through 2 disulphide bonds (9). For example, in Brazil nuts the precursor protein is 14-15 kDa in size, but the mature 2S albumin obtained from the nut extract consists of a large 10-12 kDa and a small 5 kDa subunit (13). S albumins are significantly resistant to proteolytic digestion, and to thermal and chemical denaturation (14). In a study evaluating Brazil nut 2S albumin, after 2 h of gastric digestion, approximately 25% of Ber e 1 remained intact. During duodenal digestion, residual intact 2S albumin disappeared quickly, but a modified form of the ”large fragment” remained, even after 2 h of digestion. The main immunoglobulin E epitope region of 2S albumin allergens was found to be largely intact following gastric digestion. There were also previously identified putative T-cell epitopes (17). This was similarly demonstrated with the 2S albumin in Sesame seed and Sunflower seed. Such properties are thought to be crucial for a protein both to sensitise the mucosal immune system and to provoke an allergic reaction in a sensitised individual (14,18). rBer e 1, the recombinant Brazil nut 2S albumin, is likewise resistant to digestion by pepsin (10).
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 also demonstrated in transgenic Soybean: the newly expressed protein in transgenic Soy retained its allergenicity (19-20).
A strong correlation between IgE-binding to 2S albumins and food-induced anaphylaxis has been demonstrated for Brazil nut and Sesame seeds (12). The 2S albumins may be very important in food-induced anaphylaxis, whereas minor Brazil nut allergens have been thought not to be relevant (12). However, a 15-year-old boy who experienced 2 distinct episodes of generalised urticaria about 30 minutes after eating Brazil nut had positive skin- and serum-specific IgE tests to Brazil nut but negative serum-specific IgE for Mustard, Poppy seed, Sesame seed and Sunflower seed, suggesting no sensitisation to the major 2S albumin allergen (9).
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 a high degree of similarity, from 34% between Sunflower seed and Brazil nut, to >52% similarity and >38% identity between Brazil nut and many other plant 2S albumins (21-25). The English walnut allergen (Jug r 1) exhibits a 46.1% identity with the Brazil nut 2S albumin seed storage protein Ber e 1 (25-26). A 2s albumin has also been detected in Buckwheat (27).
Cross-reactivity observed between Peanut or Walnut and Brazil nut presumably depends on other ubiquitous seed storage protein allergens, namely the vicilins. However, the major IgE-binding epitope identified on the molecular surface of the Walnut Jug r 1 allergen shared a pronounced structural homology with the corresponding region of the Pecan nut Car i 1 allergen. With the exception of Peanut, 2S albumins could thus account for the IgE-binding cross-reactivity observed between some other dietary nuts, e.g. Walnut and Pecan nut (28).
Sicherer SH, Sampson HA. Peanut and tree nut allergy.
Curr Opin Pediatr 2000;12(6):567-73
Hide DW. Clinical curio: allergy to Brazil nut. Br Med J (Clin Res Ed) 1983;287(6396):900
Gillespie DN, Nakajima S, Gleich GJ. Detection of allergy to nuts by the radioallergosorbent test.
J Allergy Clin Immunol 1976;57(4):302-9
Dutau G, Rittie JL, Rance F, Juchet A, Bremont F. New food allergies. [French] Presse Med 1999;28(28):1553-9
Ewan PW. Clinical study of peanut and nut allergy in 62 consecutive patients: new features and associations.
Arshad SH, Malmberg E, Krapf K, Hide DW. Clinical and immunological characteristics of Brazil nut allergy.
Clin Exp Allergy 1991;21(3):373-6
Borja JM, Bartolome B, Gomez E, Galindo PA, Feo F. Anaphylaxis from Brazil nut.
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
Asero R, Mistrello G, Roncarolo D, Amato S. Allergy to minor allergens of Brazil nut. Allergy 2002;57(11):1080-1
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
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
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
Roux KH, Teuber SS, Sathe SK. Tree nut allergens. Int Arch Allergy Immunol 2003;131(4):234-44
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
Asero R, Mistrello G, Roncarolo D, Amato S. Allergenic similarities of 2S albumins. Allergy 2002;57(1):62-3
Pantoja-Uceda D, Bruix M, Santoro J, Rico M, Monsalve R, Villalba M. Solution structure of allergenic 2 S albumins.
Biochem Soc Trans 2001;30(6):919-24
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
Moreno FJ, Maldonado BM, Wellner N, Mills EN. Thermostability and in vitro digestibility of a purified major allergen 2S albumin (Ses i 1) from white sesame seeds (Sesamum indicum L.). Biochim Biophys Acta 2005 Sep 25;1752(2):142-53
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
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
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
Kelly JD, Hlywka JJ, Hefle SL. Identification of sunflower seed IgE-binding proteins.
Int Arch Allergy Immunol 000;121(1):19-24
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
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
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
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
Matsumoto R, Fujino K, Nagata Y, Hashiguchi S, Ito Y, Aihara Y, Takahashi Y, Maeda K, Sugimura K. Molecular characterization of a 10-kDa buckwheat molecule reactive to allergic patients’ IgE. Acta allergologica 2004;59(5):533-8
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