Soybean

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Code: f14
Latin name: Glycine max (Soja hispida)
Source material: Dried beans
Family: Fabaceae (Leguminosae)
Common names: Soybean, Soya Bean, Soy, Soya

Allergen Exposure

Geographical distribution
Soybean is the world's most important legume. Proteins of Soybeans are widely used in animal and human nutrition.

There are more than 200 varieties of Soybean. Soya is grown for edible green pods, half-ripe seeds, and dry seeds. Pods are rough and hairy and contain 3 or 4 seeds; these are smooth and vary in colour, being black, brown, green, yellow or white. The seeds have a higher protein content than do any other edible seeds.

During seed maturation, the membranous inner epidermis of the endocarp detaches from the pericarp, or pod wall, to cover the seed, influencing to varying degrees the luster of the seed surface (1).  Different seed luster phenotypes have been described, including "shiny", "intermediate", "dull", "bloom", and "dense bloom" (2).

Soy protein consists of 136 phytochemicals (3). Soybean contains goitrogens, tannins, phytoestrogens, flatus-producing oligosaccharides, phytate, and saponins (4). Some of Soybean's phyto-chemicals have oestrogenic effects (5).

Environment
The bean can be used fresh, or can be processed into Soybean flour, flakes, grits, or Soy milk, or it can be pressed for oil. Soybeans are a primary foodstuff in Asia. Soybean oil is put to many uses. It is included in salad oil, margarine and industrial components, and in linoleum and glue in the plywood industry, where it is considered an occupational allergen. Soy sauce, or shoyu, is a fermented product of Soybean and Wheat.

Imitation cheeses may replace 30% of casein protein with Soya protein. Soya mince, a good source of protein, may be used as a replacement for meat or fish. Unlike other pulses, Soya beans have a healthy balance of amino acids and contain significant amounts of (mostly unsaturated) fat.

Unexpected exposure

Soya protein is found almost ubiquitously in processed foods, even in butter and margarine (6). In recent times, bread, including white bread, may contain Soy flour. In a Spanish study, the most frequent sources of hidden Soy allergens were boiled ham, sausages, cheese puffs, precooked dishes, desserts and gravy (7).

Reactions after unexpected food exposure
Soy proteins are frequently found in meat products, bread, and a wide range of industrially produced food products (8). Examples are Spanish sausage products (9), pizza (10), and candy containing Soy lecithin (11).

Soybean lecithin may be used in the baking industry, and baker's asthma as a result of exposure to Soybean lecithin has been described (13). Residual protein in Soy lecithin may also be involved in baker's asthma (12-13). Soybean lecithin allergy has been described in a child (11). Allergic reactions have also been reported to a Soybean protein isolate that comprised 50% of a dietary powder. Of these 20 patients, 85% were found to have IgE antibodies against Gly m 4, as well as to the major birch pollen allergen Bet v 1, suggesting an association of Birch pollen and Soy food allergy. Seventeen patients experienced facial, oropharyngeal, and/or systemic allergic symptoms within 20 minutes after ingesting the Soy product for the first time (14).

Soya bean oil is extracted from the Soybean and, if not purified, may still contain allergens, resulting in allergic reactions (15-16).

In a review of the role of hidden allergens in allergic reactions in Spanish patients, all the reactions caused by hidden allergens of legumes occurred in Soy-allergic patients, except for 1 lentil-allergic patient. Thirty-nine percent of the Soy-allergic patients had some reaction caused by Soy as a hidden allergen. The most frequent sources of hidden Soy allergens were boiled ham, sausages, cheese puffs, precooked dishes, desserts and gravy (7).

Several fatal reactions to Soy recorded in young asthmatics with known Peanut allergy but unrecognised sensitivity to Soy (17) reinforce the importance of proper labelling of food and the need for education of patients, school staff and healthcare personnel. Soybean is more frequently used as a substitute and constituent in many different foods, and therefore a higher frequency of adverse reactions to Soybean can be expected.

Interestingly, the transfer of Egg, Peanut, and Soybean sensitisation following bone marrow transplantation has been reported (18).

Allergens
Seed proteins in Soybean consist of 2 major fractions that account for 70% to 80% of the total protein: 11S albumins and 7S globulins. Approximately 6% of Soybean proteins are classified as inhibitors of trypsin and chymotrypsin, and approximately 0.5% are sugar-binding lectins. The 2 major classes of inhibitors are the Kunitz trypsin inhibitor, which inhibits trypsin, and the Bowman-Birk inhibitor, which inhibits both trypsin and chymotrypsin. These inhibitors and lectins can impair the nutritional quality and safety of Soy-based diets unless removed or inactivated (19-20).

There are at least 21 allergenic proteins in Soybean, ranging from 14 to78 kDa, that may result in IgE binding (21-24). A Kunitz trypsin inhibitor (as indicated above), glycinin, the alpha-subunit of beta-conglycinin, a P34/Gly m Bd 30K protein, a thiol protease, and a 50-kDa protein with homology to chlorophyll A-B binding protein have been identified as binding IgE of subjects with Soy allergy (20,25-27). In another study, sera of Soybean-allergic atopic dermatitis patients have been shown to recognise about 15 Soybean proteins, of which 3 were identified as major allergens: Gly m Bd 60K, Gly m Bd 30K, and Gly m Bd 28K (28).

In a study of 10 Soybean varieties, including those with a "dull" phenotype and those with a "shiny" phenotype, a 7 kDa band was present in all varieties except in those with a “shiny” phenotype. In in vitro tests, the varieties with a “shiny” phenotype contained fewer allergens than the other varieties studied. However, skin testing found no response differences among the Soybean varieties (2).

Soybean hulls also contain at least 3 unique main allergens; those with sizes of 8, 7.5, and 7 kDa have been identified (29). A large quantity of Soybean hydrophobic protein (HPS), a potentially hazardous allergen that causes asthma in Soybean dust-allergic individuals, is synthesised in the endocarp of the inner ovary wall and deposited on the seed surface during development. Its precise amount varies among Soybean cultivars and is greater on dull-seeded phenotypes (1).

During the process of harvesting, transport and storage, microbial and mold contamination can raise the temperature of Soybeans to 75 °C or higher. In a study using serum from 68 Soybean asthmatic subjects, it was demonstrated that the heat during storage and transport of Soybeans could generate 2 new allergen determinants or increase epitope exposure as a result of conformational changes. However, the clinical significance of this was not assessed (30).

Hydrolysis or fermentation of Soybean in the manufacture of fermented Soybean products, including miso, tempeh, tofu, and mold-hydrolyzed Soy sauce, has been shown to reduce allergenicity. Depending on the extent of hydrolysis or fermentation, a proportion of Soybean allergens may remain in the processed vegetable proteins (31). In a study of sera of patients with delayed hypersensitivity to fermented Soybean, 6 allergens, including 3 of 38, 28, and 26 kDa, were demonstrated (32). Properly manu-factured Soy sauce is reported to have no residual allergic activity (33).

The following allergens have been characterised:
 
  • Gly m 1, a 7-8 kDa protein, a HPS, Soybean hydrophobic protein, a major allergen (29-30,34-40).
     
  • Gly m 2, an 8 kDa protein, a major allergen (29-30,34,36,41).
     
  • Gly m 3, a 12-15 kDa protein, a profilin, a major allergen (25,34,42-44).
     
  • Gly m 4, a Bet v 1 homologue (Group 1 Fagales-related protein), a major allergen, previously known as Gly m SAM22 (14,25,34,45).
     
  • Gly m 2S Albumin, a 2S Albumin  (46-48).
     
  • Gly m 39kD, a 39 kDa protein, a major allergen (47,49).
     
  • Gly m Bd28K, a 28 kDa protein, a 7S Vicilin-like globulin, a major allergen (50-56).
     
  • Gly m Bd30K, a 30-34 kDa protein, a thiol protease of the papain superfamily, a major allergen, also known as P34. (21,26,57-66).
     
  • Gly m Lectin, lectin, SBA, an agglutinin, a major allergen (67).
     
  • Gly m Bd 60K, a 63-67 kDa protein, a major allergen (28,43).
     
  • Gly m TI, a 20 kDa protein, a trypsin inhibitor, a major allergen (27,47,68-70).
     
  • Gly m Oleosin, an oleosin (71).
     
  • Gly m IFR, an isoflavone reductase (72).
     
  • Gly m Glycinin G1, a glycinin, a major allergen (73).
     
  • Gly m Glycinin G2, a glycinin, a major allergen (73).
     
  • Gly m Glycinin G4, a glycinin, a major allergen (73).

A class 1 chitinase has been isolated from Soybean seed coat (74). Its allergenicity was not assessed.

Different Soybean allergens are involved in inhalation and food allergy. Furthermore, the allergens involved in occupational asthma caused by Soybean flour are predominantly high-molecular-weight proteins that are present in both the hull and flour of Soybeans; they are different from the allergens that cause asthma outbreaks from Soybean dust, allergens that are mainly low-molecular-weight proteins concentrated in the hull, e.g., Gly m 1 (36,75). Airborne Soybean hull proteins are known causes of asthma epidemics around harbours and Soy processing plants, whereas Soy flour dust proteins may cause occupational allergy in food and feed industries (76). Individuals in rural areas where Soybean is grown and harvested may also be exposed to Soybean dust by inhalation (77).

Nonetheless, heterogenous sensitisation to Soybean allergens appears to occur. An evaluation was done of the main Soybean hull allergens using the sera of 18 asthmatic patients affected by the Soybean dust asthma epidemic in Barcelona. allergen-specific IgE in 15 of the 18 (83.3%) sera was demonstrated. In 11 sera, allergens of 8, 7.5 and 7 kDa were detected, which are the molecular weights described for Gly m 2, Gly m 1A and Gly m 1B, respectively. In 3 sera, an allergen with an estimated size of 8.2-8.3 kDa and 4 others of 25-36 kDa were detected. The study confirmed that Soybean hulls contain major allergens and additional higher-molecular-weight allergens, which selectively bind specific IgE of the sera that do not react with the 3 low-molecular-weight components; there is a dichotomous and non-overlapping pattern (29). The same authors demonstrated that in occupational asthma in Soybean-exposed bakers, IgE-binding occurs mainly to high-molecular-weight allergens: none of the patients showed IgE-reactivity against the low-molecular-weight protein Gly m 1, and only 1 patient showed IgE-reactivity to the Soybean hull allergen Gly m 2 (36).

Similarly, in a recent study to determine the clinical characteristics of Soy allergy in Europe, the pattern of IgE reactivity against proteins with molecular weights of between approximately 10 and 70 kDa was highly individual among the patients and did not correlate with the severity of symptoms (78).

In Soybean food allergy, the most important allergen is a protein termed P34 (Gly m Bd30K), which is abundant in the seeds and other parts of the plant (2).

The low-molecular-weight Soybean allergens Gly m 1 and Gly m 2 are found in Soybean dust. Gly m 1, although abundant in Soybean dust, occurs in all parts of the Soybean plant at all stages of growth; but the telae (hulls) and pods are by far the richest source (79). These 2 allergens were shown to be responsible for epidemic asthma outbreaks resulting from Soy dust (36).

Gly m 1 occurs in the form of isoallergens named Gly m IA (protein S2) and Gly m IB (protein S1), which were recognised by IgE antibodies from 95% of patients who suffered asthma attacks during these asthma outbreaks of 1987 and 1988 in Cartagena, Spain (39).

Gly m 3 is a profilin, a panallergen. In a study of serum from 13 Soybean-sensitised subjects, IgE antibodies to recombinant Gly m 3 was detected in 9 (69%) (43).

A study was done of 22 patients allergic to Birch pollen who also had Soy allergy, and among whom 10 experienced symptoms localised to the oral cavity, while 6 had a more severe reaction following a Soy challenge. Gly m 4-specific IgE was found in 96% (21/22) of the patients. All patients had Bet v 1-specific IgE antibodies, and 23% (5/22) had positive Bet v 2 results. Gly m 4 is a Bet v 1 homologue. In IgE immuno-blotting, 25% (6/22) of the patients recognised Gly m 3 (profilin), and 64% (14/22) recognised other Soy proteins. IgE binding to Soy was at least 80% inhibited by Birch pollen and 60% inhibited by rGly m 4 in 9 of 11 sera tested. Seventy-one percent (67/94) of highly Bet v 1-sensitised patients with Birch pollen allergy were sensitised to Gly m 4, and 9 (9.6%) of those patients reported Soy allergy, confirming that Soybean is a Birch pollen-related allergenic food. The authors concluded that Gly m 4 is the major Soy allergen for patients allergic to Birch pollen who also have Soy allergy (25).

Similarly, in a study investigating IgE-mediated reactions to a Soy-containing diet food product in patients allergic to Birch pollen, significant IgE binding was demonstrated to the Soy isolate rSAM22 (rGly m 4) in 17 of 20 patients. Other allergenic proteins of 17 kDa (15/20), 22 kDa (1/20), and 35 to 38 kDa (2/20) were also isolated from the Soy isolate (14).

Targeting Gly m 4 in diagnostic assessment may facilitate an improvement of diagnostic sensitivity. This substance was used as a allergen-specific reagent in a study of 22 individuals with pollen-related allergy to Soybean. While only 10 out of the 22 (45%) showed positive in a Soybean extract-based test, all but 1 (96%) showed IgE binding to rGly m 4 coupled to streptavidin-coupled ImmunoCAP tests (25,80).

Soybean seeds contain a pair of 2S albumin storage proteins, AL1 and AL3. These 2S albumins were shown to be stable to heat and chemical treatments (46). Soybean 2S albumins have been reported to be minor allergens in a British patient population assessed (48).

Gly m Bd 28 K is a major Soybean glycoprotein allergen. It was originally identified as a 28 kDa polypeptide in Soybean seed flour. In a study of sera from Soy-sensitised adults, all sera contained IgE antibodies that recognised the C-terminal region of this allergen. Gly m Bd 28 K contains 2 cupin domains (56).

Gly m Bd 30K is also known as a Soybean oil-body-associated glycoprotein that is homologous to Der p (or Der f) 1, a major allergen of House dust mite, classified under the Papain superfamily (28). Gly m Bd 30K (P34) is an outlying member of the Papain superfamily of cysteine proteases. It is expressed in developing Soybean seeds and may be involved in the defence against Pseudomonas infection. P34 was reported to be the major allergen of Soybean seed and is present in processed food products that contain Soybean protein. In an evaluation of Soybean accessions, all contained similar levels of P34. Wild relatives of Soybean were also shown to contain P34. Extracts from all were shown to bind IgE antibodies from patients with clinically significant Soybean allergy (66).

Sensitisation to Gly m TI, a trypsin inhibitor, was evaluated in 14 bakers suffering from workplace-related respiratory symptoms and sensitised to Soybean. Gly m TI was found to be a major inhalant Soybean allergen, recognised by IgE antibodies in sera of 86% of the group. The Soybean lipoxidase was also found to be a major allergen in this group (69).

Soybean trypsin inhibitor was also evaluated in sera of 5 patients with atopic dermatitis and a positive food challenge to Soybean, and found to bind to IgE antibodies in only 20% of these patients (27).

Soybean oleosins are a family of small proteins involved in the formation of Soybean oil bodies; they are similar to Peanut oleosins. Oil bodies are small organelles that hold the reserve oils of seeds and consist mainly of triglycerides, phospholipids, and a few polypeptides (21). In a study of IgE binding with Peanut oleosin, the phenomenon was demonstrated in 3 of 14 sera of patients who had suffered an allergic reaction to Peanut; the main reacting bands had a molecular size estimated at approximately 34 kDa, approximately 50 kDa and approximately 68 kDa, and the size was thought to correspond to oleosin oligomers. The same occurred with crude Soybean oil fractions, with 2 bands of 16.5 and 24 kDa corresponding to monomers, and 2 bands of 50 kDa and 76 kDa corresponding to dimers and trimers, respectively (71).

Soybean glycinin and beta-conglycinin represent up to a third of protein in Soybean. Glycinin and beta-conglycinin have been characterised as major Soybean allergens involved in food hypersensitivity (81). Soy glycinin is resistant to processing (82) and stable to degradation by simulated gastric fluid (83).

The 70 kDa subunit of beta-conglycinin was shown to be recognised by 25% of Soybean-sensitive patients with atopic dermatitis. Data suggests that at least 1 epitope is located within a non-glycosylated fragment consisting of about 50 amino acid residues. The beta-conglycinin alpha subunit has been demonstrated to be able to induce anaphylaxis through an IgE mediated mechanism (73).

The storage protein glycinin accounts for about 35% of the protein content of the Soybean. It consists of 6 subunits, each of them consisting of 2 peptide chains (1 acidic and 1 basic) held together by disulfide bonds (84). The acidic peptides were found to be responsible for much but not all of the IgE binding activity of glycinin.

Potential cross-reactivity

Earlier studies of Soybean demonstrated several antigenic components with considerable cross-reactivity with other legume family members (85). While the clinical usefulness of eliminating legumes from the diet of allergic patients is disputed, several reports confirm cross-reactivity. A patient who suffered adverse reactions when eating Peas, Lentils, Peanuts, Kidney, Lima and Navy beans experienced the most severe episodes following ingestion of Soybean products (86). A specific IgE antibody response to the Kunitz Soybean trypsin inhibitor polypeptide was demonstrated.

Patients experiencing IgE-mediated symptoms after ingestion of Pea, Bean, Lentil, Peanut and Soybean have been reported, but no single patient was allergic to all (87). Similarly, in a study of Soybean sensitive-children, a high correlation of concomitant sensitisation to Pea (38/50) and Peanut (41/50) was reported (88). However, though studies have reported in vitro cross-reactivity between Peanut and other legumes, e.g. Pea, Kidney beans, and Lentil, this was not supported by clinical challenge (89). Similarly, in 22 patients who experienced adverse reactions to Lentils, 14 also had experienced immediate allergic reactions to Chick pea, and 10 to Peanut; none had experienced adverse effects to Soy or Soy-derived products. Yet all were shown to have allergy-specific IgE to all 4 legumes (90).

It has been suggested that individuals allergic to both Peanut and Soybean have IgE antibodies binding preferentially to the larger proteins, while the antibodies of those reacting only to Soybean bind strongly to proteins in the lower-molecular-weight range (22,24). Studies on 2 patients both allergic to Peanut and Soy showed extensive cross-reactivity between the 2 legume seeds (91). Several major Peanut allergens have been shown to share epitopes with Soy storage proteins. (For further information, see Peanut f13.)

An 8 kDa allergen prepared from Soybean hull shows 71% homology with a storage protein from Cow pea and 64% homology with a protein from Pea. A 17 kDa Soy allergen has also been found to cross-react with a Pea allergen (92).

It is therefore apparent that Soy-allergic individuals may be sensitised to Soybean and a number of other legumes, but may be clinically unaffected by any or all of these legumes unless a particular cross-reactive Soybean panallergen is involved.

Soybean contains a number of cross-reactive panallergens that have been characterised and may explain the patterns of co-sensitisation reported previously. With recent advances in diagnostics, the precise diagnosis of the specific Soy allergens involved may allow the deduction of potential sensitisation to other legume family members that contain the homologous allergen.

For example, Gly m 3, a profilin, is a panallergen. In a study of serum from 13 Soybean-sensitised subjects, IgE antibodies to recombinant Gly m 3 was detected in 9 (69%). The rGly m 3 cross-reacted with Bet v 2, the Birch tree pollen profilin. IgE binding to Bet v 2 could be inhibited by rGly m 3 (43).

A study was done of 22 Birch pollen-allergic patients also allergic to Soy. During food challenge, 10 patients experienced oral allergy syndrome, and 6 patients had a more severe reaction. Gly m 4-specific IgE was found in 96% (21/22) of the patients. All patients had Bet v 1-specific IgE antibodies, and 23% (5/22) had positive Bet v 2 results. In IgE immunoblotting, 25% (6/22) of the patients recognised Soy profilin (Gly m 3), and 64% (14/22) recognised other Soy proteins. IgE binding to Soy was at least 80% inhibited by Birch pollen and 60% inhibited by rGly m 4 in 9 of 11 sera tested. Seventy-one percent (67/94) of highly Bet v 1-sensitised patients with Birch pollen allergy were sensitised to Gly m 4, and 9 (9.6%) of those patients reported Soy allergy. The authors concluded that these results confirmed that Soybean is another Birch pollen-related allergenic food and that Gly m 4 was the major allergen for patients allergic to Birch pollen and also Soy (25). In a further study, in which the authors assessed 10 Mung bean-allergic subjects with concomitant respiratory allergy to Birch tree pollen for sensitisation to Vig r 1, a Bet v 1-homolous allergen, it was reported that 90% were sensitised to Gly m 4 (93). Further evidence for Bet v 1-homologue cross-reactivity was demonstrated between Gly m 4, Ara h 8 from Peanut, and Pru av 1 from Cherry (45).

In a report on 3 patients who experienced anaphylaxis to a Soy drink, cross-reactivity of Soy protein with Birch pollen allergens was identified as the cause of their severe reactions. The authors suggested that patients with Birch pollen allergy should avoid the intake of Soy protein (94).

Soybean glycinin G1 acidic chain has been reported to share IgE epitopes with Ara h 3 from Peanut, with a sequence similarity of 62% between the Soy glycinin and Ara h 3 from Peanut (95).

Soybean-specific IgE has also been reported to be cross-reactive with Potato. SPT evaluation for Soybean and fresh Potato was performed in 177 children of less than 4 years of age who were suspected of having food allergy. Further, sera from 17 children with suspected Potato allergy and 12 children with suspected Soy allergy were evaluated for IgE antibodies to natural Sola t 2-4 and Kunitz-type Soybean trypsin inhibitor (KSTI). Skin reactivity for Soybean was demonstrated in 10/177 (5%) and for Potato in 14 (7%). Of those with positive SPT for Potato, 70% had IgE antibodies to KSTI and 75% to Soybean. However, of those suspected of having allergy to Soybean, 9 (75%) had IgE antibodies to Sola t 2-4. Cross-inhibition was demonstrated for Sola t 2-4 and KSTI. The study concluded that children with suspected food allergy frequently have SPT reactivity for Soybean and Potato; and it may be due to cross-reactive IgE antibodies against structurally altered Potato allergens, and vice versa: and that this should be considered when examining children suspected of having Soybean or Potato allergy (96).

Clinical Experience

IgE-mediated reactions
Soybean may commonly induce symptoms of food allergy in sensitised individuals. Dust from Soybean storage or transport has been reported to result in exacerbation of asthma, and dust from Soybean flour may precipitate asthma in bakers (36,77).

There are 2 main types of Soy food-allergenic reactions. IgE-mediated reactions may result in respiratory, cutaneous, and gastrointestinal symptoms, and anaphylaxis. Delayed non-IgE-mediated reactions, including Soy-induced enterocolitis, may be experienced (21,97-98).

Soybean is often cited as one of the foods to which children experience IgE-mediated reactions (99-100). The prevalence of Soy bean sensitisation in a group of 317 Italian children (median age 5 months) with symptoms suggesting food allergy was 22% (101.) In another study, 37/78 (47%) of Australian children with Cow's milk allergy were reported to react to Soy at a follow-up 5 years later (102).

In an analysis of 580 French patients with reactions to food, of whom 60 presented with severe, near-fatal reactions, Soybean was implicated in 30%, the fifth most common cause after Wheat (39%), Peanut (37%), Crab (34%), and Celery (30%) (103).

Recent studies have also focussed on threshold levels that precipitate symptoms. In a recent study to determine the clinical characteristics of Soy allergy in Europe, Soy-allergic patients underwent a titrated, double-blind, placebo-controlled food challenge. All patients but 1 responded primarily with subjective symptoms to the challenge, followed by objective symptoms in 11 subjects, with symptoms ranging from rhinitis up to a decrease in blood pressure. Cumulative threshold doses for allergic reactions ranged from 10 mg to 50 g for subjective symptoms and from 454 mg to 50 g for objective symptoms. The study concluded that in a statistical model, 1% of patients with Soy allergy would react subjectively with 0.21 mg of Soy protein, and objectively with 37.2 mg of Soy protein, and that both the clinical and immunologic bases of Soy allergy in Europe are highly complex. None of the patients with Soy allergy reacted to the starting dose of 2 mg of Soy (1 mg of Soy protein) (78). An earlier statistical model projected that 0.3 g of Soy flour will elicit an allergic response in 1 out of every 100 Soy-sensitive people (104).

A number of studies concluded that Soybean, among other foods, may be a common food allergen in atopic dermatitis in children (105). In 165 American patients aged 4 months to 22 years and having atopic dermatitis, 7 foods (Milk, Egg, Peanut, Soy, Wheat, Cod/Catfish, Cashew) accounted for 89% of the positive challenges (106). In an American study, 28% of 53 Soy-sensitive children with atopic dermatitis exhibited an allergic response after ingesting less than 0.5 g of Soy flour. This corresponds to approximately 41 mg of Soy protein (107).

There is evidence that Soy allergens may pass to infants through breast milk, resulting in sensitisation. In a study of a selected population of 59 predominantly breast-fed young Australian infants (mean age 26.5 weeks) who had moderate to severe generalised atopic dermatitis, 53 infants (90%) had demonstrable skin reactivity to 1 or more of the 5 common food allergens (Egg white, Cow's milk, Peanut, Wheat or Soy), and 80% were positive to Egg white (108).

The fact that Soy reactions are not always obviously immediate may confuse the interpretation of challenge tests. In a re-challenge of 18 Australian infants who had stabilised after feeding with a non-allergenic diet, 12 were found to react to formulas that previously had not been tolerated. The infants (median age 7 1/2 months) were given Neocate formula for 2 months and then underwent a 7-day double-blind placebo-controlled challenge with the formula previously best tolerated. In 12 of the 18 infants, irritability, vomiting, diarrhoea, and/or eczema flares developed during the challenge. However, only 2 showed immediate symptoms. In the remaining 10, symptoms evolved after 4 to 7 days of challenge. Adverse reactions occurred to a Soy formula in 6 patients, to Whey hydrolysate in 2, and to Casein hydrolysate in 4 (109).

Although Soybean is considered a "classical food allergen" (89), it has long been regarded as a safe food substitute for children showing adverse reactions to Cow's milk. However, about a fourth of Cow's milk-sensitive patients may become allergic to Soy protein (110-111). It was found that Soy formula did not lower the cumulative incidence of atopic disease, as compared with Cow's milk (112). Breast-feeding or less allergenic formulas should be preferred, but socioeconomic conditions and other risk factors should be considered (113-114).

Soybean ingestion may result in anaphylaxis, inducing respiratory, cutaneous, cardiovascular, and gastro-intestinal symptoms, and even death (115-116). Soybean food-dependant exercise-induced anaphylaxis has been reported (117). Authors have cautioned that Soy protein may be an underestimated cause of food anaphylaxis. In a study of anaphylactic reactions to Soy, the majority of patients had a symptom-free period of 30-90 minutes between the early mild symptoms and the later severe and rapidly worsening asthma (17).

Anaphylaxis to fermented Soybean has also been reported. Researchers have hypothesised that the mechanism of late-onset anaphylaxis to fermented Soybeans is delayed absorption or release into the bowel rather than an immunologic phenomenon. In a Japanese study of 2 patients with demonstrable skin reactivity to fermented Soybean and IgE antibodies to Soybean, challenge with 50 g of fermented Soybeans caused generalised urticaria and dyspnoea 13 hours later in 1 patient. Plasma histamine and tryptase levels were transiently elevated during the anaphylactic event (118).
Anaphylaxis had also been reported following ingestion of Soy drink in 3 German individuals. The authors concluded that the cause of the severe Soy reactions was cross-reactivity of Soy protein with Birch pollen allergens. The authors suggested that patients with Birch pollen allergy should avoid the intake of Soy protein (94). Other authors have also concluded that Birch pollen and Soybean hypersensitivity may occur as a result of cross-reactivity; they hold that Gly m 4, a Bet v 1-homologue, is the allergen causing Soy-related symptoms. Symptoms caused by different Soy-based commercial products ranged from OAS to anaphylaxis (25).

In studies in Japan, IgE antibodies to Soybean were measured by the Pharmacia CAP System (119-121). Sensitivity and specificity were 100% and 87%, respectively (119).

Soy dust asthma and epidemic asthma
The allergens involved in causing asthma outbreaks are mainly low-molecular-weight proteins concentrated in the hull, whereas the allergens involved in occupational asthma caused by Soybean flour are predominantly high-molecular-weight proteins that are present both in the hull and flour (36).

Epidemic asthma in areas around harbours where Soybeans are unloaded from ships has been reported from Barcelona (122), Cartagena (123), Tarragona (124), Valencia (125), A Coruña (125), Naples (126), New Orleans (127), and New Zealand (128). A large number of fatal cases, probably resulting from anaphylaxis, were recorded. The major allergens involved were found in the hull of the bean (although they are also present in other parts of the bean) (37,41,79,123-124,129). All the asthmatic epidemic patients from Barcelona were shown to have IgE antibodies for Soybean (129), and the prevalence of Soybean sensitivity in the Cartagena incident was reported to be 89% (130). Soybean hull antigens were also shown to be involved in hypersensitivity pneumonitis (131), and irritant effects of Soy dust may contribute to the development of respiratory problems in Soy mill workers (132).

As this suggests, Soybean hull dust may also occur at work (for example, in storage areas) and may result in occupational asthma without flour-related broncho-constriction (133).

Soy dust allergens have been shown to be sporadically present in the air in a region where Soybeans are extensively grown, and were most prevalent during the harvest period. The highest level recorded was 73 ng/m3 (35).

Rhinitis, conjunctivitis and broncho-spasm following the inhalation of Soybean dust from a “bean bag” toy have been reported (134).

Baker's asthma
Occupational asthma in bakers, millers and workers in food processing plants may be caused by Soy flour. The reported prevalence of Soy sensitisation in bakers with workplace-related respiratory symptoms ranges from 19% (135) to 25% (36,136).

The Soybean allergens causing occupational asthma in exposed bakers were investigated and compared with those involved in epidemic asthma. The subjects were 4 bakers and confectioners with work-related respiratory symptoms who were exposed to Soybean flour. Sensitisation to Soybean flour was demonstrated by allergen-specific IgE evaluation and was confirmed by positive bronchial challenge tests, which elicited immediate or dual asthmatic responses. IgE-binding occurred mainly to high-molecular-weight allergens, and no one showed IgE-reactivity against the predominant hull allergen Gly m 1. Only 1 patient showed IgE-reactivity to the Soybean hull allergen Gly m 2. The study concluded that these bakery workers had developed IgE-mediated occupational asthma to Soybean flour and that the allergens involved in occupational asthma caused by Soybean flour are predominantly high-MW proteins that are present both in the hull and flour; and that these allergens are different from the allergens causing asthma outbreaks, which are mainly low-MW proteins concentrated in the hull (36).

Animal food processing plant workers may also come into contact with Soybean flour, resulting in sensitisation. In 35 men working in an animal food processing plant, the most frequent sensitisation was to fish flour (82.9%), followed by carotene (77.1%), Corn (65.7%), Four-leaf clover (62.9%), Sunflower (54.3%), Chicken meat (31.4%), Soy (28.6%), and Yeast (22.7%). (137) There may be a long delay between the initial contact and subsequent sensitisation, as described in a 43-year-old woman who developed asthma 6 years after beginning work in a food-processing plant in which Soybean flour was used as a protein extender. Symptoms of sneezing, coughing, and wheezing would begin within minutes of exposure to Soybean flour and resolve 2 hours after exposure ceased (92).

Other reactions
Food protein-induced enterocolitis (FPIES) in infants as a result of Soy ingestion has been reported by a number of authors. Cow's milk is also a prominent cause, although other foods may also be implicated (138-140). FPIES is a severe cell-mediated gastrointestinal food hypersensitivity and is characterised by symptoms occurring several hours after ingestion of a food or foods. Symptoms typically begin in the first month of life along with failure to thrive and may progress to acidemia and shock. Typical symptoms of FPIES are delayed (median 2 hours) and include vomiting, diarrhoea, lethargy and dehydration (141). Resolution of symptoms occurs after removal of the causal protein from the diet, but symptoms recur with a characteristic pattern on re-exposure. Approximately 2 hours after reintroduction of the protein, vomiting ensues, followed by an elevation of the peripheral blood polymorphonuclear leukocyte count and diarrhoea. Lethargy and hypotension may also occur. IgE antibodies to the causal food is generally not present (140,142). An early study on a small group of children with “Soy intolerance” (suspected enterocholitis) was not conclusive in terms of the role of antibodies, although IgE antibodies to several fractions were found. The source and quality of the Soy protein used in challenge tests was not declared (143). It has been proposed that the presence of IgE antibodies to the allergen involved may be helpful in predicting long-lasting sensitivity (140).

Eosinophilic esophagitis is a disorder identified in patients with symptoms suggestive of gastroesophageal reflux disease but unresponsive to conventional reflux therapies. In a study of 146 patients diagnosed as having eosinophilic esophagitis, as evaluated by skin prick and atopy patch testing, Egg, Cow's Milk, and Soy sensitivity were identified most frequently by skin prick testing, whereas Corn, Soy, and Wheat sensitivity were identified most frequently with atopy patch testing. In more than 75% of patients with eosinophilic esophagitis, both outward symptoms and esophageal inflammation were significantly improved with dietary elimination of foods (144).

Symptoms of allergy to Soy may be atypical. A 39-year-old woman was reported who complained of respiratory symptoms such as dry cough and mild dyspnoea occurring after the ingestion of food containing Soya (145). An association between recurrent serous otitis media and food allergy has been described in 81 of 104 patients. An elimination diet resulted in a significant amelioration of the disease in 86% of the patients, and a challenge diet provoked recurrence of symptoms in 94%. The highest frequency of sensitivity was seen with Milk, Wheat, Egg, Peanut, Soy and Corn (146).

After measuring Soy-specific IgA and IgG antibodies in children with Soy intolerance and with coeliac disease, investigators concluded that the observed increase of IgA antibodies correlated to mucosal injury, while the increase of IgG antibodies was related to the increase of antigen entry (147).
Mold contamination of Soybean may occur with storage and transport and theoretically may result in sensitisation, depending on the organism involved (30). Aflatoxins have been reported in Soybeans (148).

Various Wheat and Soy protein sources, including the Soy protein isolates used to make infant formulas, have been said to be causally involved in to juvenile or insulin-dependent diabetes mellitus (IDDM) (149).

Unexpected allergens from other organisms may someday occur in Soy. Progress in biotechnology, which allows the introduction of alien genes for the purpose of improving properties of crops, has opened the way for new potential allergy risks. The fact that alien allergens can be and have been introduced into Soybean (150) has stimulated the discussion of potential changes of allergenicity in transgenic food (151-152). But it is obvious that the analysis of potential risks for sensitisation is difficult until a human population has been exposed.

Compiled by Dr Harris Steinman, harris@zingsolutions.com

References

  1. Gijzen M, Miller S, Kuflu K, Buzzell R, Miki B. Hydrophobic protein synthesized in the pod endocarp adheres to the seed surface.
  2. Plant Physiol 1999;120:951-9
  3. Codina R, Ardusso L, Lockey RF, Crisci C, Medina I. Allergenicity of varieties of soybean. Allergy 2003;58(12):1293-8
  4. Fang N, Yu S, Badger TM. Comprehensive phytochemical profile of soy protein isolate.
  5. J Agric Food Chem 2004;52(12):4012-20
  6. Liener IE Implications of antinutritional components in soybean foods.
  7. Crit Rev Food Sci Nutr 1994;34(1):31-67
  8. Albertazzi P, Pansisini F, Banaccorsi G, et al. The effects of dietary soy supplementation on hot flashes. Obstet Gynecol 1998;91:6-11
  9. Yokota S, Takahashi Y, Aihara Y, Kurihara K, Suguro H, Matsuyama S. Immunologic analysis of milk, hen egg, and soybean proteins in butter and margarine, and clinical assessment for availability of hypoallergenic margarine (HAM). [Japanese] Arerugi 1996;45(12):1237-43
  10. Anibarro B, Seoane FJ, Mugica MV. Involvement of hidden allergens in food allergic reactions. J Investig Allergol Clin Immunol 2007;17(3):168-72
  11. Malmheden Yman I. Food-induced hypersensitivity reactions: a survey over the last 5 years. Allergologie 1995;18:403
  12. Pérez Carral C, Vidal C, Chomón B. An unsuspected source of Soybean exposure. Allergy 1996;51:85
  13. Senna GB, Crivellaro M, Bonadonna P, Dama A, Mezzelani P, Passalacqua G. Pizza, an unsuspected source of soybean allergen exposure. Allergy 1998;53:1106-7
  14. Renaud C, Cardiet C, Dupont C. Allergy to Soy lecithin in a cChild. J Pediatr Gastroenterol Nutr 1996;22:328-9
  15. Müller U, Weber W, Hoffmann A, Franke S, Lange R, Vieths S. Commercial soybean lecithins: a source of hidden allergens?
  16. Z Lebensm Unters Forsch A 1998;207:341-51
  17. Lavaud F, Perdu D, Prévost A, Vallerand H, Cossart C, Passemard F. Baker's asthma related to soybean lecithin exposure.
  18. Allergy 1994;49:159-62
  19. Kleine-Tebbe J, Vogel L, Crowell DN, Haustein UF, Vieths S. Severe oral allergy syndrome and anaphylactic reactions caused by a Bet v 1- related PR-10 protein in soybean, SAM22. J Allergy Clin Immunol 2002;110(5):797-804
  20. Steinman HA. Hidden Allergens in Foods.
  21. J Allergy Clin Immunol 1996;98(2):241-50
  22. Porras O, Carlsson B, Fällström SP, Hanson LÅ. Detection of soy protein in soy lecithin, margarine and, occasionally soy oil.
  23. Int Archs Allergy Appl Immun 1985;78:30-2
  24. Foucard T, Malmheden Yman I. A study on severe food reactions in Sweden – is soy protein an underestimated cause of food anaphylaxis? Allergy 1999;54(3):261-5
  25. Bellou A, Kanny G, Fremont S, Moneret-Vautrin DA Transfer of atopy following bone marrow transplantation. Ann Allergy Asthma Immunol 1997;78(5):513-6
  26. Brandon DL, Friedman M. Immunoassays of soy proteins.
  27. J Agric Food Chem 2002;50(22):6635-42
  28. Helm RM, Cockrell G, Herman E, Burks WA, Sampson HA, Bannon GA. Cellular and molecular characterization of a major soybean allergen.
  29. Int Arch Allergy Immunol 1998;117:29-37
  30. Wilson S, Blaschek K, de Mejia E. Allergenic proteins in soybean: processing and reduction of P34 allergenicity.
  31. Nutr Rev 2005;63(2):47-58
  32. Herian AM, Taylor SL, Bush RK. Identification of soybean allergens by immunoblotting with sera from soy-allergic adults. Int Arch Allergy Appl Immunol 1990;92:193-8
  33. Ogawa T, Bando N, Tsuji H, Okajima H, Nishikawa K, Sasaoka K. Investigation of the IgE-binding proteins in soybeans by immunoblotting with the sera of the soybean-sensitive patients with atopic dermatitis.
  34. J Nutr. Sci Vitaminol 1991;37:555-65
  35. Awazuhara H, Kawai H, Maruchi N. Major allergens in soybean and clinical significance of IgG4 antibodies investigated by IgE- and IgG4-immunoblotting with sera from soybean-sensitive patients.
  36. Clin Exp Allergy 1997;27:325-32
  37. Mittag D, Vieths S, Vogel L, Becker WM, Rihs HP, Helbling A, Wuthrich B, Ballmer-Weber BK. Soybean allergy in patients allergic to birch pollen: clinical investigation and molecular characterization of allergens.
  38. J Allergy Clin Immunol 2004;113(1):148-54
  39. Helm RM, Cockrell G, Connaughton C, West CM, Herman E, Sampson HA, Bannon GA, Burks AW. Mutational analysis of the IgE-binding epitopes of P34/Gly m Bd 30K. J Allergy Clin Immunol 2000;105(2 Pt 1):378-84
  40. Burks WA, Cockrell G, Connaughton C, Guin J, Allen W, Helm RM. Identification of peanut agglutinin and soybean trypsin inhibitor as minor legume allergens.
  41. Int Arch Allergy Immunol 1994;105:143-9
  42. Ogawa A, Samoto M, Takahashi K. Soybean allergens and hypoallergenic soybean products. J Nutr Sci Vitaminol (Tokyo) 2000;46(6):271-9
  43. Codina R, Lockey RF, Fernandez-Caldas E, Rama R. Identification of the soybean hull allergens responsible for the Barcelona asthma outbreaks. Int Arch Allergy Immunol 1999;119(1):69-71
  44. Codina R, Oehling AG Jr, Lockey RF. Neoallergens in heated soybean hull. Int Arch Allergy Immunol 1998;117(2):120-5
  45. Herian AM, Taylor SL, Bush RK. Allergenic reactivity of various soybean products as determined by RAST inhibition.
  46. J Food Science 1993;58:385-8
  47. Inomata N, Osuna H, Kawano K, Yamaguchi J, Yanagimachi M, Matsukura S, Ikezawa Z. Late-onset Anaphylaxis after Ingestion of Bacillus Subtilis-fermented Soybeans (Natto): Clinical Review of 7 Patients. Allergol Int 2007;56(3):257-61
  48. Kobayashi M. Immunological functions of soy sauce: hypoallergenicity and antiallergic activity of soy sauce.
  49. J Biosci Bioeng 2005;100(2):144-51
  50. International Union of Immunological Societies Allergen Nomenclature: IUIS official list http://www.allergen.org/List.htm 2007
  51. Gijzen M, Gonzalez R, Barber D, Polo F. Levels of airborne Gly m 1 in regions of soybean cultivation.
  52. J Allergy Clin Immunol 2003;112(4):803-5
  53. Quirce S, Polo F, Figueredo E, Gonzalez R, Sastre J. Occupational asthma caused by soybean flour in bakers – differences with soybean-induced epidemic asthma.
  54. Clin Exp Allergy 2000 Jun;30(6):839-46
  55. Gonzalez R, Varela J, Carreira J, Polo F. Soybean hydrophobic protein and soybean hull allergy. Lancet 1995;346:48-9
  56. Baud F, Pebay-Peyroula E, Cohen-Addad C, Odani S, Lehmann MS. Crystal structure of hydrophobic protein from soybean; a member of a new cysteine-rich family.
  57. J Mol Biol 1993;231(3):877-87
  58. Gonzalez R, Polo F, Zapatero L, Caravaca F, Carreira J. Purification and characterization of major inhalant allergens from soybean hulls. Clin Exp Allergy 1992;22(8):748-55
  59. Odani S, Koide T, Ono T, Seto Y, Tanaka T. Soybean hydrophobic protein. Isolation, partial characterization and the complete primary structure.
  60. Eur J Biochem 1987;162(3):485-91
  61. Codina R, Lockey RF, Fernandez-Caldas E, Rama R. Purification and characterization of a soybean hull allergen responsible for the Barcelona asthma outbreaks. II. Purification and sequencing of the Gly m 2 allergen.
  62. Clin Exp Allergy 1997;27(4):424-30
  63. Martinez A, Asturias JA, Monteseirin J, Moreno V, Garcia-Cubillana A, Hernandez M, de la Calle A, Sanchez-Hernandez C, Perez-Formoso JL, Conde J. The allergenic relevance of profilin (Ole e 2) from Olea europaea pollen.
  64. Allergy 2002;57 Suppl 71:17-23
  65. Rihs HP, Chen Z, Rueff F, Petersen A, Rozynek P, Heimann H, Baur X IgE binding of the recombinant allergen soybean profilin (rGly m 3) is mediated by conformational epitopes. J Allergy Clin Immunol 1999;104(6):1293-301
  66. van Ree R, Voitenko V, et al. Profilin is a cross-reactive allergen in pollen and vegetable foods. Int Arch Allergy Immunol 1992;98(2):97-104
  67. Mittag D, Batori V, Neudecker P, Wiche R, Friis EP, Ballmer-Weber BK, Vieths S, Roggen EL. A novel approach for investigation of specific and cross-reactive IgE epitopes on Bet v 1 and homologous food allergens in individual patients.
  68. Mol Immunol 2006;43(3):268-78
  69. Lin J, Fido R, Shewry P, Archer DB, Alcocer MJ. The expression and processing of two recombinant 2S albumins from soybean (Glycine max) in the yeast Pichia pastoris. Biochim Biophys Acta 2004;1698(2):203-12
  70. Gu X, Beardslee T, Zeece M, Sarath G, Markwell J. Identification of IgE-Binding Proteins in Soy Lecithin. Int Arch Allergy Immunol 2001;126(3):218-25
  71. Lin J, Shewry PR, Archer DB, Beyer K, Niggemann B, Haas H, Wilson P, Alcocer MJ. The potential allergenicity of two 2S Albumins from soybean (Glycine max): A protein microarray approach. Int Arch Allergy Immunol 2006;141(2):91-102
  72. Natarajan SS, Xu C, Bae H, Caperna TJ, Garrett WM. Characterization of storage proteins in wild (Glycine soja) and cultivated (Glycine max) soybean seeds using proteomic analysis.
  73. J Agric Food Chem 2006;54(8):3114-20
  74. Hiemori M, Ito H, Kimoto M, Yamashita H, Nishizawa K, Maruyama N, Utsumi S, Tsuji H. Identification of the 23-kDa peptide derived from the precursor of Gly m Bd 28K, a major soybean allergen, as a new allergen. Biochim Biophys Acta 2004;1675(1-3):174-83
  75. Tsuji H, Hiemori M, Kimoto M, Yamashita H, Kobatake R, Adachi M, Fukuda T, Bando N, Okita M, Utsumi S. Cloning of cDNA encoding a soybean allergen, Gly m Bd 28K. Biochim Biophys Acta 2001;1518(1-2):178-82
  76. Hiemori M, Bando N, Ogawa T, Shimada H, Tsuji H, Yamanishi R, Terao J. Occurrence of IgE antibody-recognizing N-linked glycan moiety of a soybean allergen, Gly m Bd 28K. Int Arch Allergy Immunol 2000;122(4):238-45
  77. Tsuji H, Bando N, Hiemori M, Yamanishi R, Kimoto M, Nishikawa K, Ogawa T. Purification of characterization of soybean allergen Gly m Bd 28K. Biosci Biotechnol Biochem 1997;61(6):942-7
  78. Ogawa T, Bando N, Tsuji H, Nishikawa K, Kitamura K. Alpha-subunit of beta-conglycinin, an allergenic protein recognized by IgE antibodies of soybean-sensitive patients with atopic dermatitis. Biosci Biotechnol Biochem 1995;59(5):831-3
  79. Bittencourt AL, Fernandes I, Pereira IRO, Honmoto CS, Tanaka MK, Lima FSP, Abdalla DSP. Detection of 7S and 11S soy protein fractions by monoclonal antibody-based immunoassays in food.
  80. Food Agricul Immunol 2005;16(2):91-100
  81. Xiang P, Haas EJ, Zeece MG, Markwell J, Sarath G. C-Terminal 23 kDa polypeptide of soybean Gly m Bd 28 K is a potential allergen. Planta 2004;220(1):56-63
  82. Babiker EE, Azakami H, Ogawa T, Kato A. Immunological characterization of recombinant soy protein allergen produced by Escherichia coli expression system.
  83. J Agric Food Chem 2000;48(2):571-5
  84. Samoto M, Miyazaki C, Akasaka T, Mori H, Kawamura Y. Specific binding of allergenic soybean protein Gly m Bd 30K with alpha'- and alpha-subunits of conglycinin in soy milk. Biosci Biotechnol Biochem 1996;60(6):1006-10
  85. Bando N, Tsuji H, Yamanishi R, Nio N, Ogawa T. Identification of the glycosylation site of a major soybean allergen, Gly m Bd 30K. Biosci Biotechnol Biochem 1996;60(2):347-8
  86. Tsuji H, Okada N, Yamanishi R, Bando N, Kimoto M, Ogawa T. Measurement of
  87. Gly m Bd 30K, a major soybean allergen, in soybean products by a sandwich enzyme-linked immunosorbent assay. Biosci Biotechnol Biochem 1995;59(1):150-1
  88. Ogawa T, Tsuji H, Bando N, Kitamura K, Zhu YL, Hirano H, Nishikawa K. Identification of the soybean allergenic protein, Gly m Bd 30K, with the soybean seed 34-kDa oil-body-associated protein. Biosci Biotechnol Biochem 1993;57(6):1030-3
  89. Tsuji H, Bando N, Kimoto M, Okada N, Ogawa T. Preparation and application of monoclonal antibodies for a sandwich enzyme-linked immunosorbent assay of the major soybean allergen, Gly m Bd 30K.
  90. J Nutr Sci Vitaminol (Tokyo) 1993;39(4):389-97
  91. Hosoyama H, Obata A, Bando N, Tsuji H, Ogawa T. Epitope analysis of soybean major allergen Gly m Bd 30K recognized by the mouse monoclonal antibody using overlapping peptides. Biosci Biotechnol Biochem 1996;60(7):1181-2
  92. Yamanishi R, Tsuji H, Bando N, Yoshimoto I, Ogawa T. Micro-assay method for evaluating the allergenicity of the major soybean allergen, Gly m Bd 30K, with mouse antiserum and RBL-2H3 cells. Biosci Biotechnol Biochem 1997;61(1):19-23
  93. Herman E. Soybean allergenicity and suppression of the immunodominant allergen. Crop Sci 2005;45:462-7
  94. Yaklick RW, Helm RM, Cockrell G, Herman EM. Analysis of the distribution of the major soybean seed allergens in a core collection of Glycine max accessions.
  95. Crop Sci 1999;39:1444-7
  96. Fu TJ, Abbott UR, Hatzos C. Digestibility of food allergens and nonallergenic proteins in simulated gastric fluid and simulated intestinal fluid-a comparative study.
  97. J Agric Food Chem 2002;50(24):7154-60
  98. De La Barca AM, Wall A, Lopez-Diaz JA. Allergenicity, trypsin inhibitor activity and nutritive quality of enzymatically modified soy proteins.
  99. Int J Food Sci Nutr 2005;56(3):203-11
  100. Baur X, Pau M, Czuppon A, Fruhmann G. Characterization of soybean allergens causing sensitization of occupationally exposed bakers. Allergy 1996;51(5):326-30
  101. Takagi K, Teshima R, Okunuki H, Sawada J. Comparative study of in vitro digestibility of food proteins and effect of preheating on the digestion.
  102. Biol Pharm Bull 2003;26(7):969-73
  103. Pons L, Chery C, Romano A, Namour F, Artesani MC, Gueant JL. The 18 kDa peanut oleosin is a candidate allergen for IgE-mediated reactions to peanuts.
  104. Allergy 2002;57 Suppl 72:88-93
  105. Karamloo F, Wangorsch A, Kasahara H, Davin LB, Haustein D, Lewis NG, Vieths S. Phenylcoumaran benzylic ether and isoflavonoid reductases are a new class of cross-reactive allergens in birch pollen, fruits and vegetables.
  106. Eur J Biochem 2001;268(20):5310-20
  107. Guo P, Piao X, Cao Y, Ou D, Li D. Recombinant soybean protein beta-conglycinin alpha'-subunit expression and induced hypersensitivity reaction in rats. Int Arch Allergy Immunol 2007;145(2):102-10
  108. Gijzen M, Kuflu K, Qutob D, Chernys JT. A class I chitinase from soybean seed coat.
  109. J Exp Bot 2001;52(365):2283-9
  110. Gomez-Olles S, Cruz MJ, Renstrom A, Doekes G, Morell F, Rodrigo MJ. An amplified sandwich EIA for the measurement of soy aeroallergens.
  111. Clin Exp Allergy 2006;36(9):1176-83
  112. Gomez-Olles S, Cruz MJ, Bogdanovic J, Wouters IM, Doekes G, Sander I, Morell F, Rodrigo MJ. Assessment of soy aeroallergen levels in different work environments.
  113. Clin Exp Allergy 2007;37(12):1863-72
  114. Codina R, Ardusso L, Lockey RF, Crisci CD, Jaen C, Bertoya NH. Identification of the soybean hull allergens involved in sensitization to soybean dust in a rural population from Argentina and N-terminal sequence of a major 50 KD allergen.
  115. Clin Exp Allergy 2002;32(7):1059-63
  116. Ballmer-Weber BK, Holzhauser T, Scibilia J, Mittag D, Zisa G, Ortolani C, Oesterballe M, Poulsen LK, Vieths S, Bindslev-Jensen C. Clinical characteristics of soybean allergy in Europe: A double-blind, placebo-controlled food challenge study. J Allergy Clin Immunol 2007;119(6):1489-96
  117. Swanson MC, Li JT, Wentz-Murtha PE, Trudeau WL, Fernandez-Caldas E, Greife A, Rodrigo MA, Morell F, Reed CE. Source of the aeroallergen of soybean dust: a low molecular mass glycopeptide from the soybean tela.
  118. J Allergy Clin Immunol 1991;87(4):783-8
  119. Lidholm J, Ballmer-Weber BK, Mari A, Vieths S. Component-resolved diagnostics in food allergy. Curr Opin Allergy Clin Immunol 2006;6(3):234-40
  120. Liu X, Feng J, Xu ZR, Wang YZ, Liu JX. Oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta-conglycinin.
  121. Clin Exp Allergy 2008 Feb;38(2):350-6
  122. Adachi M, Kanamori J, Masuda T, Yagasaki K, Kitamura K, Mikami B, Utsumi S. Crystal structure of soybean 11S globulin: glycinin A3B4 homohexamer. Proc Natl Acad Sci USA 2003;100(12):7395-400
  123. Astwood JD, Leach JN, Fuchs RL. Stability of food allergens to digestion in vitro.
  124. Nature Biotech 1996;14:1269-73
  125. Djurtoft R, Pedersen HS, Aabin B, Barkholt V. Studies of food allergens: Soybean and egg proteins.
  126. Adv Exp Med Biology 1991;289:281-93
  127. Crawford LV, Roan J, Triplett F, Hanissian AS. Immunologic studies on the legume family of foods. Ann Allergy 1965;23:303-8
  128. Moroz LA, Yang WH. Kunitz soybean trypsin inhibitor; A specific allergen in food anaphylaxis. N Eng J Med 1980;302:1126-8
  129. Gall H, Forck G, Kalveram KJ, et al. Immediate type allergy to legume food. [German]. Allergologie 1990;13:352-5
  130. Bardare M, Magnolfi C, Zani G. Soy sensitivity: personal observation on 71 children with food intolerance.
  131. Allerg Immunol (Paris) 1988;20:63-6
  132. Yunginger JW. Classical food allergens. Allergy Proc. 1990;11:7-9
  133. Belver MT, Pascual CY, Pereira MJ, Valls A, Garcia Ara MC, Boyano T, Martin Esteban M. Cross-reactivity between lentils and chickpeas towards peanuts and soy, in a Spanish children population. [Poster: XXI Congress of EAACI] Allergy 2002;57 Suppl 73:79-84
  134. Eigenmann PA, Burks WA, Bannon GA, Sampson HA. Identification of unique peanut and soy allergens in sera adsorbed with cross-reacting antibodies. J Allergy and Clin Immunol 1996;98:969-78
  135. Bush RK, Schroeckenstein D, Meier-Davis S, Balmes J, Rempel D. Soybean flour asthma: detection of allergens by immunoblotting.
  136. J Allergy Clin Immunol 1988;82(2):251-5
  137. Mittag D, Vieths S, Vogel L, Wagner-Loew D, Starke A, Hunziker P, Becker WM, Ballmer-Weber BK. Birch pollen-related food allergy to legumes: identification and characterization of the Bet v 1 homologue in mungbean (Vigna radiata), Vig r 1.
  138. Clin Exp Allergy 2005;35(8):8-1055
  139. Süss A, Rytter M, Sticherling M, Simon JC. Anaphylactic reaction to soy drink in three patients with birch pollen allergy. [German] J Dtsch Dermatol Ges 2005;3(11):895-7
  140. Beardslee TA, Zeece MG, Sarath G, Markwell JP. Soybean glycinin G1 acidic chain shares IgE epitopes with peanut allergen Ara h 3. Int Arch Allergy Immunol 2000;123(4):299-307
  141. Seppa¨la¨ U, Majamaa H, Turjanmaa K, Vanto T, Kalkkinen N, Palosuo T, Reunala T. Frequent skin prick test sensitivity to soy and potato in children: cross-reactivity to structurally-related allergens? [Poster: XXI Congress of EAACI] Allergy 2002;57 Suppl 73:79-84
  142. Taylor SL, Kabourek JL. Soyfoods and allergies: Separating fact from fiction.
  143. The Soy Connection 2003;11:1-6
  144. Sampson HA. Food anaphylaxis.
  145. Br Med Bull 2000;56(4):925-35
  146. Anderson JA. Pediatrician's guide to food allergy. Henry Ford Hosp Med J 1988;36:198-203
  147. Sampson HA. Food hypersensitivity as a pathogenic factor in atopic dermatitis.
  148. NER Allergy Proc. 1986;7:511-9
  149. Giampietro PG, Ragno V, Daniele S, Cantani A, Ferrara M, Businco L. Soy Hypersensitivity in children with food allergy.
  150. Ann Allergy 1992;69:143-6
  151. Bishop JM, Hill DJ, Hosking CS. Natural history of cow milk allergy; Clinical outcome. J Pediatr 1990;116:862-7
  152. Andre F, Andre C, Colin L, Cacaraci F, Cavagna S. Role of new allergens and of allergens consumption in the increased incidence of food sensitizations in France. Toxicology 1994;93(1):77-83
  153. Bindslev-Jensen C, Briggs D, Osterballe M. Can we determine a threshold level for allergenic foods by statistical analysis of published data in the literature?
  154. Allergy 2002;57(8):741-6
  155. Hannuksela M. Diagnosis of dermatologic food allergy.
  156. Ann Allergy 1987;59(5 Pt 2):153-6
  157. Burks AW, James JM, Hiegel A, Wilson G, Wheeler JG, Jones SM, Zuerlein N. Atopic dermatitis and food hypersensitivity reactions. J Pediatr 1998;132(1):132-6
  158. Sicherer SH, Morrow EH, Sampson HA. Dose-response in double-blind, placebo-controlled oral food challenges in children with atopic dermatitis. J Allergy Clin Immunol 2000;105(3):582-6
  159. Rennick GJ, Moore E, Orchard DC. Skin prick testing to food allergens in breast-fed young infants with moderate to severe atopic dermatitis.
  160. Australas J Dermatol 2006;47(1):41-45
  161. Hill DJ, Cameron DJ, Francis DE, Gonzalez-Andaya AM, Hosking CS. Challenge confirmation of late-onset reactions to extensively hydrolyzed formulas in infants with multiple food protein intolerance.
  162. J Allergy Clin Immunol 1995;96:386-94
  163. Zeiger RS. Challenges in the prevention of allergic disease in infancy.
  164. Clin Rev Allergy 1987;5:349-73
  165. Lee EJ, Heiner DC. Allergy to cow milk-1985. Pediatrics in review 1986;7:195-203
  166. Chandra RK. Five-Year Follow-Up of High-Risk Infants with Family History of Allergy Who Were Exclusively Breast-Fed or Fed Partial Whey Hydrolysate, Soy, and Conventional Cow's Milk Formulas.
  167. J Pediatr Gastroenterol Nutr 1997;24:380-8
  168. Kerner JA Jr. Use of Infant Formulas in Preventing or Postponing Atopic Manifestations.
  169. J Pediatr Gastroenterol Nutr 1997;24:442-6
  170. Kerner JA Jr. Formula Allergy and Intolerance. Gastroenterology Clinics of North America 1995;24:1-25
  171. Foucard T, Edberg U, Malmheden Yman I. Fatal and severe food hypersensitivity. Peanut and soya underestimated allergens. [Swedish] Lakartidningen 1997;94(30-31):2635-8
  172. David TJ. Anaphylactic shock during elimination diets for severe atopic eczema. Arch Dis Child 1984;59:983-6
  173. Guinnepain MT, Eloit C, Raffard M, Brunet Moret MJ, et al. Exercise-induced anaphylaxis: useful screening of food sensitization. Ann Allergy 1996;77(6):491-6
  174. Inomata N, Osuna H, Yanagimachi M, Ikezawa Z. Late-onset anaphylaxis to fermented soybeans: the first confirmation of food-induced, late-onset anaphylaxis by provocation test. Ann Allergy Asthma Immunol 2005;94(3):402-6
  175. Okudaira H, Ito K, Miyamoto T, Wagatsuma Y, Matsuyama R, Kobayashi S et al. Evaluation of new system for the detection of IgE antibodies (CAP) in atopic disease.
  176. Aerugi 1991;40:544-54
  177. Sumimoto S, Kawi M, Kasajima Y, Hamamoto T. Study on specific IgE antibodies in pediatric allergic patients by CAP System.
  178. Aerugi 1990;39:1416-21
  179. Yoshimoto A et al. Relationship between the total IgE levels and specific IgE antibodies. Radioisotopes 1990;39:445-8
  180. Sunyer J, Anto JM, Rodrigo M-J, Morell F. Case-control study of serum immunoglobulin-E antibodies reactive with soybean in epidemic asthma.

 

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