Soybean

Allergen Exposure

Unexpected exposure

• 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

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