Latin name: Hordeum vulgare
Source material: Untreated planting seeds
Family: Poaceae (Gramineae)
Common names: Barley, Barleycorn
This hardy cereal grain is native to Mesopotamia, and its use dates back to the Stone Age. Barley is the fourth most important grain in the world, after Wheat, Maize and Rice. Most of the Barley now grown in the Western world is used either for animal fodder or, when malted, in the brewing and distilling industries. Barley is an erect annual grass, producing grain in bristly-bearded terminal spikes.
About half of the total US production is used for malting, but because of Barley's mild flavour and soft texture, the grain is often found in soups and baby foods. Malt is used in making several kinds of alcoholic beverages, most prominently beer and whiskey. Other products are flour, flakes and bran. Scotch and Hulled barley are types with only the outer husk removed. Pearl barley is rounded and polished after the husk is removed. Barley flour is ground from Pearl barley and must be combined with a Gluten-containing flour for use in yeast breads. When combined with water and lemon, Pearl barley is used to make Barley water, an old-fashioned restorative for invalids. Barley is a good source of B vitamins and some minerals.
A number of allergens have been isolated from Barley. In 132 Pig farm-workers, 43 showed IgE reactivity to 15 components of Barley with molecular masses ranging from 14 kDa to 148 kDa. The major allergen appeared to be a 37 kDa protein and was found in 32 (74.4%) of the 43 immunoblot-positive serum samples. Components of about 55 and 67 kDa reacted with 26 (60.5%) and 18 (41.9%) of the positive serum samples, respectively (1). These proteins may be similar to those in a study reporting that Barley flour proteins of 69, 52 and 10 kDa had been identified in serum from Wheat-hypersensitive individuals and appeared to be major allergens (2).
A number of allergens have been characterised:
- Hor v 15, a 16 kDa protein, previously known as Hor v 1, an alpha-amylase/trypsin inhibitor (3-12).
- Hor v 16, an alpha-amylase (3,13)
- Hor v 17, a beta-amylase (3).
- Hor v 21, also known as hordein (3,14-15).
- Hor v LTP, a 10 kDa protein, a lipid transfer protein (7,9,14,16).
- Hor v Z4, a 45 kDa protein (9,14).
The allergens Hor v 1, Hor v 2, Hor v 4, Hor v 5, Hor v 9 (now known as Hor v 5), Hor v 12 and Hor v 13 have been isolated and characterised from Barley pollen.
Barley seed proteins that could be involved in the foaming properties of beer were investigated. From Barley to Malt and to beer, most of the heat-stable proteins were reported to be disulfide-rich defence proteins, e.g., serpin-like chymotrypsin inhibitors (protein Z), amylase and amylase-protease inhibitors, and lipid transfer proteins (14). The main residual allergens in beer that may result in allergic reactions are the residual lipid transfer protein allergen or Hor v Z4 from Barley (7,9). In individuals who experienced urticaria from beer, analysis of their sera demonstrated that IgE bound only a 10 kDa protein (found also in Malt). In sera of the control patient group, individuals with baker's asthma from Barley flour, a 16 kDa allergen was implicated. Because of the severity of the allergic manifestations to beer, the researchers recommend testing for sensitivity to this beverage those atopic patients who are positive to Malt/Barley and/or who exhibit urticarial reactions after drinking beer (7).
In the case of a 21-year-old atopic woman who developed urticaria, angioedema of the face, a wheeze and dyspnoea shortly after drinking beer and after eating a Maize snack, immunoblotting demonstrated several IgE-binding bands at 31-56 kDa in Malt and Barley extracts, and a major band at 38 kDa in the beer extract (17).
Furthermore, Gluten from Barley can be present in beer, as a result of the addition of Malt. However, a study demonstrated that Gluten levels decreased due to precipitation during the mashing process, during primary and secondary fermentation and, lastly, as a result of adsorption during beer stabilisation. The Gluten content in beer was approximately 3 orders of magnitude lower than in the raw Malt (18).
In baker's asthma, where Barley is implicated, Hor v 15, an alpha-Amylase/Trypsin inhibitor has been shown to be a major allergen (6,8,12).
The major Wheat allergen associated with exercise-induced anaphylaxis is an omega-5 gliadin. Gamma-70 and gamma-35 secalins in Rye and gamma-3 hordein, or Hor v 21, in Barley have been shown to cross-react with omega-5 gliadin, suggesting that Rye and Barley may also elicit symptoms in patients with Wheat-dependent, exercise-induced anaphylaxis (15).
Barley lipid transfer protein (LTP1) is a heat-stable and protease-resistant albumin that concentrates in beer, where it participates in the formation and stability of beer foam. Whereas Barley LTP1 does not display any foaming properties, the corresponding beer protein is surface-active as a result of glycation by Maillard reactions on malting, acylation on mashing, and structural unfolding on brewing (19). Barley LTP (and protein Z(4)) have been identified as the main beer allergens (9).
An extensive cross-reactivity among the different individual species of the genus could be expected (20). Cross-reactivity with other species within the Poaceae family can be expected, as well as with other species within the genus Triticum.
RAST inhibition tests have demonstrated cross-antigenicity among different cereal grains. The degree of cross-reactivity closely paralleled their taxonomic relationship and appeared to be in the following order of decreasing closeness: Wheat, Triticale, Rye, Barley, Oat, Rice and Maize (21).
Other studies have demonstrated cross-allergenicity between Rye and Barley, and among Wheat, Rye and Barley. The major allergen was thought to be Gluten, although 16 similar protein bands were detected that were common to all 3 (22-23). Similarly, in patients sensitised to Wheat and Rye flour, IgE antibody investigation indicated that there is significant cross-reaction with seed extracts of Wheat, Durum wheat, Triticale, Rye, Barley, Rye grass, Oats, Canary grass, Rice, Maize, Sorghum and Johnson grass, compared with non-related plants. In particular, significant cross-reactivity was shown among grain extracts of Wheat, Rye, Barley and Oats. Results of this study suggested that the bran layers of cereal grains are at least as allergenic as the flour (24). The clinical relevance of this is demonstrated in a study of 5 patients with cereal-dependent exercise-induced ana-phylaxis and IgE antibodies to Wheat, Rye, Barley and Oats. Wheat gliadin and the corresponding ethanol-soluble proteins of taxonomically closely related cereals were found to be the causative allergens (25). However, in a study examining the IgE specificity of Wheat, Barley and Rye proteins through the use of 2 sera as representative of patients with either Wheat-dependent exercise-induced anaphylaxis (WDEIA) or hypersensitivity to hydrolysed Wheat proteins (HHWP), IgE from a patient with both contact urticaria and food allergy to Gluten hydrolysates cross-reacted with gamma 3-hordein. The pattern of reactivity with Wheat, Barley and Rye proteins differed from that of a WDEIA patient tested under the same conditions (26).
Furthermore, although pollen from these cereals contains unique and specific allergens, the existence of cross-reactivity between Barley and Wheat flour, and between Rye and Wheat flour, as well as among the pollens of cereals and cereal flours, has been suggested (27).
Cross-reactivity among plants containing lipid transfer protein (LTP) is possible but would depend on the specific plants. For example, the lipid transfer protein from Maize was shown to completely cross-react with Rice and Peach lipid transfer proteins but not with Wheat or Barley lipid transfer proteins (17). Rice nonspecific lipid transfer protein closely resembles nonspecific LTPs of Wheat, Barley and Maize, exhibiting a nearly identical pattern of the numerous sequence-specific interactions (28).
A number of Wheat and Barley flour proteins that belong to the cereal alpha-amylase/trypsin inhibitor family have been identified as major allergens associated with baker's asthma. There is complete cross-reactivity among grass, Wheat, Barley, and Rice trypsin inhibitors (13,17,29). However, different allergenic behaviours have been reported to occur among such homologous allergens from Rye, Barley, and Wheat (30).
Cereal alpha- and beta-amylase appear to be important allergens in patients with allergy to flour. RAST inhibition studies have shown minimal cross-reactivity between Barley alpha- or beta-amylase and Barley and fungal alpha-amylase. An association was demonstrated between IgE antibodies to Wheat flour and to Barley alpha-amylase and Barley beta-amylase, but a poor association with fungal alpha-amylase (31).
Gamma-70 and gamma-35 secalins in Rye, and gamma-3 hordein (probably representing Hor v 21) in Barley, have been shown to cross-react with omega-5 gliadin, a major allergen in Wheat-dependent, exercise-induced anaphylaxis (WDEIA). These findings suggest that Rye and Barley may also elicit symptoms in patients with Wheat-dependent, exercise-induced ana-phylaxis (15). Due to this cross-reactivity, treatment with a Gluten-free diet, i.e., a diet excluding Wheat, Rye, and Barley, is indicated for all patients with WDEIA (32).
Prolamines extracted from Wheat (gliadin), Rye (secalin), Barley (hordein) and Oats (avenin) were used to raise antibodies in rabbits. The close botanical relationship between Wheat and Rye, and, to a lesser extent, between these and Barley, is clearly established. The cross-reactivity of gliadin, secalin and hordein with anti-avenin serum was found to be weak. In contrast, avenin shows a strong cross-reactivity with anti-gliadin serum (33).
A degree of homology among amylase/protease inhibitors, acyl-CoA oxidase and fructose-bisphosphate-aldolase from Wheat, Barley, Maize, and Rice has been reported but requires further elucidation (34).
Barley may commonly induce symptoms of food allergy in sensitised individuals. (1) Symptoms may include gastrointestinal distress, atopic dermatitis and urticaria, angioedema, anaphylaxis and food-dependant, exercise-induced anaphylaxis, wheezing and baker's asthma. Cough, wheezing, shortness of breath, fever, stuffy nose, and skin itching/rash on exposure to grain dust have also been reported, as well as "grain fever" (35).
In a study of cereal allergy and atopic dermatitis, on oral provocation, 18 children exhibited a positive response to Wheat, 3 to Rye, 1 to Barley, and 1 to Oats. Symptoms were dermatologic, gastrointestinal, or oropharyngeal, and their onset after provocation was immediate in 8, delayed in 14, and both immediate and delayed in 1. A combination of SPT, IgE antibody determination and histamine-release tests detected all those with immediate reactions and 9/14 with delayed reactions. Of 5 subjects negative to these tests, 3 were positive on patch or lymphocyte proliferation tests (36).
In a study evaluating the allergic reactivity to ingested and inhaled cereal allergens at different ages among 66 patients, 40 children aged 3 to 6 months experienced diarrhoea, vomiting, eczema or weight loss after the introduction of cereal formula into their diet. Coeliac disease was excluded in all. The most important allergen was Wheat, followed by Barley and Rye. Among adults with cereal allergy, sensitisation to other allergens was common, especially to Lolium perenne (Rye grass) pollen (37).
Anaphylaxis following the ingestion of Barley may occur. These reactions may be to residual Barley proteins in beer. In 2 cases of severe systemic reactions due to beer ingestion, 1 required emergency care, and the other presented with generalised urticaria and angioedema (38). A 21-year-old woman is described who developed urticaria, angioedema of the face, a wheeze and dyspnoea shortly after drinking beer and after eating a Maize snack. She was shown on immunoblotting studies of her serum to have antibodies to allergens in Malt and Barley extracts present in the beer. The authors concluded that the patient had developed type I hypersensitivity to Barley, Malt and Maize (18).
Food-dependent exercise-induced ana-phylaxis may result from ingestion of Barley (15,39). In 5 patients with cereal-dependent exercise-induced anaphylaxis and IgE antibodies to Wheat, Rye, Barley and Oats, Wheat gliadin and the corresponding ethanol-soluble proteins of taxonomically closely related cereals were found to be the causative allergens (26). Thus, Rye and Barley may elicit these symptoms in patients with Wheat-dependent, exercise-induced anaphylaxis, and vice versa (15). Due to this cross-reactivity, treatment with a Gluten-free diet, i.e., a diet excluding Wheat, Rye, and Barley, is indicated for all patients with WDEIA. In an evaluation of sera of 2 patients with either Wheat-dependent exercise-induced anaphylaxis (WDEIA) or hyper-sensitivity to hydrolysed wheat proteins, in the latter patient, who experienced both contact urticaria and food allergy to Gluten hydrolysates, IgE was shown to also cross-react with gamma 3-hordein (Hor v 21) (27).
Barley may also result in occupational allergy in bakery and other food industry workers, liqueur and spirit manufacturers, and farmers. Barley may commonly result in baker's asthma (28). Barley alpha-amylase/trypsin inhibitors have been identified as major allergens associated with baker's asthma (30). Asthma related to exposure to cereal flour contained in animal formula feeds has been reported (40). Similarly, flour made from Barley resulted in IgE-mediated occupational respiratory symptoms in Pig farm workers in southern Taiwan (1).
Occupational asthma paired with asthma following oral ingestion of Barley flour and beer made from Barley has also been reported. A 50-year-old man developed asthma both after exposure to feeding stuffs and flours and after ingestion of beverages made of cereal flour. Allergy to Barley flour (and Maize flour and mites) was demonstrated by skin reactivity and allergen-specific IgE. A bronchial challenge test with Barley flour resulted in an immediate positive response (41).
Cereal flours are used in the wood industry to improve the quality of the glues necessary to produce veneer panels in wood manufacturing. Three workers were found to be allergic to cereal alpha-amylase inhibitors, proteins cross-reactive proteins found in Rye, Barley and Wheat (4).
Occupational asthma may also occur to Barley grain dust. A report was made of a 32-year-old storeman who dealt with the packaging of Wheat flour, Barley and Peanuts. He developed immediate symptoms of sneezing, cough and dyspnoea on exposure to Barley (42).
Alpha-amylase allergens have been identified as a major allergen in baker's asthma (12).
Barley may result in or exacerbate atopic dermatitis (24) or contact dermatitis (43).
Barley may also cause coeliac disease, an autoimmune disease resulting in a food-induced enteropathy, which occurs following exposure to prolamins (Gluten) in Wheat, Rye, and Barley (44-45).
Infantile food protein-induced enterocolitis syndrome (FPIES) is a severe, cell-mediated gastrointestinal food hypersensitivity typically provoked by Cow's milk or Soy but sometimes by other foods, including Barley. Symptoms of typical FPIES are delayed (median: 2 hours) and include vomiting, diarrhoea, lethargy and dehydration. Initial presentation is severe in 79% of patients, prompting evaluation for sepsis and hospitalisation for dehydration or shock. FPIES appears not to occur to maternally ingested foods through breastfeeding, but does occur if the offending food is fed directly to the infant (46).
The ingestion, by a largely illiterate population in Iraq, of Wheat and Barley seed treated with an alkyl mercury fungicide for sowing led to a major outbreak of poisoning with a high fatality rate (47).
Six cases of acute exogenous allergic alveolitis after loading mouldy Barley have been reported (48).
Malt, a product of Barley, may result in immediate-type reactions. (See Malt f90.) Malt extract is made from germinating Barley. In a patient allergic to Malt, the allergic reactions usually occurred after consumption of Malt-containing chocolate drinks and Malt-containing snack products (18,49).
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