Further Reading

Cultivated rye g12

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Code: f5
Latin name: Secale cereale
Source material: Untreated planting seeds
Family: Poaceae (Gramineae)
Common names: Rye, Rogge

There is a need to differentiate between Rye the foodstuff (Secale cereale), Cultivated Rye grass pollen (Secale cereale) g12, Rye grass pollen (Lolium perenne) g5, and Wild Rye grass pollen (Elymus tricoides) g70. This distantly related genus, Elymus, contains species known as Wild Ryes, which are used as cover and for forage. A Wheat hybrid is known as Giant Rye.

Allergen Exposure

Geographical distribution
Rye, a hardy, tufted annual grass 1-1.5 m tall, was probably native to south-western Asia but is now widely cultivated in the temperate regions of the world (often where conditions are unfavourable for Wheat), where it is used mostly as a bread grain and as a livestock feed. It is grown especially extensively in northern Europe and Asia. It apparently co-evolved with Wheat and Barley for over 2,000 years until its value for food was recognised. But it has many other uses. Rye is taller but similar in habit to Wheat, reaching 0.5 to 1.2 m, with a nodding, longer, more slender, somewhat terminal spike.

Less than 50% of the Rye grown in the U.S. is harvested for grain, with the remainder used as pasture, hay, silage or as a cover crop. About half of the amount harvested for grain is used for livestock feed or exported, and the remainder is used for alcoholic beverages, food, and seed.

Rye is used in bread making, alcoholic fermentation, and as feed for livestock. The straw may be useful for thatching.

The grain is used to make flour, the importance of which is second only to Wheat flour. Although Rye flour does not develop true gluten, it has proteins that give it the capacity for making leavened bread; which is, however, denser and usually darker than Wheat bread. Rye is usually mixed with 25 to 50% Wheat flour for bread making. Rye bread is especially popular in northern Europe. Rye can also be used to make cakes, etc. The seed can be sprouted and added to salads. The roasted grains are a substitute for coffee.

Malt, a sweet substance produced by germinating the seed, is extracted from the roasted germinated seed and used as a sweetening agent and in making beer, etc. Canadian and United States whiskies are made mainly from Rye.

The grains are used in folk remedies for tumours and other cancers. They are reported to be laxative.

Unexpected exposure
See under Environment. The straw is used as a fuel; for thatching, paper-making, weaving hats, mats, etc.; as a packing material for nursery stock, bricks and tiles; for bedding, paper manufacture, archery targets, and mushroom compost. Rye flour is frequently used in the wood industry to increase the viscosity of the glue employed to manufacture boards (1).


The following allergens have been isolated:

  • Sec c 12, a profilin (2).
  • Sec c 20, a secalin (3-7).
  • Sec c a A TI, a 13.5 kDa alpha-amylases/trypsin inhibitor (8-10).
  • Sec c 1, Sec c 2, Sec c 4, Sec c 5, Sec c 12 and Sec c 13 have been characterised in Cultivated rye grass pollen and contribute to asthma, allergic rhinitis and allergic conjunctivitis from exposure to this pollen. Sec c 12, a profilin, has been detected in both Rye seed and Cultivated rye pollen (1). See Cultivated rye grass g12.

Rye seed contains the panallergen profilin, but at much lower levels than found in Rye pollen and in other foods such as Celery or Tomato (1), and may be of low clinical significance, as heat processing will destroy the protein. Nonetheless, profilin in Rye seed may play a role in occupational asthma, caused by bakers inhaling Rye flour or dust.

Various other allergenic proteins have been detected but not characterised.

Using IgE-immunoblotting analysis and serum samples from 40 adult patients with allergy to cereals (35 patients with atopic dermatitis, 1 with rhinitis and 4 with urticaria), polyspecific binding patterns were demonstrated with each cereal; Rye exhibited 35 bands. The most common protein binding to patients' sera (16/35, 46%) was a 40 kDa protein. There were 16 similar proteins detected in Wheat, Rye and Barley extracts, suggesting cross-reactivity among these cereals (11). Rye flour proteins of 21 and 12 kDa have been identified as major allergens in serum from Wheat-hypersensitive individuals (12).

The major Wheat allergen associated with exercise-induced anaphylaxis is an omega-5 gliadin. Similar allergens have been detected in Rye. Through SPT with these allergens in Rye, gamma-70 secalin was detected in 10/15 (67%) of patients, to gamma-35 secalin in 3/15 (20%) patients, and to gamma-3 hordein in 7/15 (47%) patients (3).

The salt-soluble proteins of Wheat and Rye flour dust are considered the most relevant allergens in Baker's asthma (9,13). Members of the cereal alpha-amylase/trypsin inhibitor family are main allergens involved in allergic reactions to cereal flours. However, different allergenic behaviours were found among homologous allergens from Rye, Barley, and Wheat (7-8). Three Rye proteins, namely Sec c 1, RDAI-1 and RDAI-3, were shown to provoke positive SPT in more than 50% of Rye-allergic patients, although the serum IgE antibody levels were lower (7-8). Franken et al. isolated 2 allergens with molecular weights of 35 and 14 kDa in water-soluble Rye flour extracts using immunoblotting techniques on sera from 100 bakers (14). Garcia-Casado et al. isolated a protein of about 13.5 kDa from Rye flour. This allergen may be the same as the 14 kDa allergen isolated by Franken et al. This protein provoked positive skin-specific IgE responses in 15/21 (71%) patients with Baker's asthma (9).

In 2 bakery workers with baker's asthma caused mainly by exposure to Rye flour, Rye flour immunoblotting showed IgE-binding bands of around 12-15 kDa that correspond to Rye flour enzymatic inhibitors and that were not present in the Wheat flour immunoblot (15).

In a report describing occupational allergy to Rye flour in 9 wood workers who were exposed to wood dust and experienced asthma and/or rhinoconjuncitivis, implicated allergens were 3 purified Rye allergens belonging to the cereal alpha-amylase inhibitor family, and in particular Sec c 1 (8/9 patients) (1). These inhibitors, as well as their Wheat and Barley homologues, have been identified as prominent allergens associated with baker's asthma (10).

Six distinct gamma- and omega-type secalins, together with 2 low-molecular-mass glycoproteins, have been identified as the major coeliac immunoreactive proteins from Rye endosperm. A group of secalins has been isolated: an omega-type secalin of 40 kDa (omega 1-40); 3 gamma-type secalins, a 70 kDa (gamma-70), 2 35 kDa (gamma-35) proteins, and 2 low-molecular-mass glycoproteins of 15 and 18 kDa. These proteins are also involved in non-IgE mediated coeliac disease (4). It appears that the presence of IgA and IgG antibodies to different cereal antigens is a result of natural exposure and in atopic dermatitis displays little diagnostic significance, in contrast to antigliadin antibody response in dermatitis herpetiformis and coeliac disease (16).

Class I and class II chitinases have been isolated from Rye seed. The chitinase accumulates in the seed during the later stage of development. The allergenic potential was not evaluated (17-18).

Antifreeze proteins, which are proteins that have the ability to retard ice crystal growth, have been identified as the most abundant apoplastic proteins in cold-acclimated winter Rye leaves. All tests indicated that these antifreeze proteins are similar to members of 3 classes of pathogenesis-related proteins, namely, endochitinases, endo-beta-1,3-glucanases, and thaumatin-like proteins (19).

Potential cross-reactivity

An extensive cross-reactivity among the different individual species of the genus could be expected (20). By using RAST inhibition tests, cross-antigenicity was shown to exist between different cereal grains: Rye, Wheat, Triticale, Barley, Oat, Maize and Rice. 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. The allergenic activity in the Rye and Wheat extracts was found to be distributed among various fractions of different molecular weights (21). Other studies have documented cross-reactivity between Rye and Wheat (22), and Rice may cross-react with Rye, Maize, Wheat and Rye pollen (23). Cross-reactivity between Rye and Rye pollen has been shown, as they both contain the Sec c 1 (b) allergen (7-8). Cross-reactivity has also been demonstrated among grain extracts of Wheat, Rye, Barley and Oats. The results of the study suggested that the bran layers of cereal grains are at least as allergenic as the flour derived from the grain (24).

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. Members of the Rye alpha-amylase inhibitor family are main allergens involved in allergic reactions to cereal flours. In a study comparing the allergenic potential among the homologous allergens from Rye, Barley, and Wheat, different degrees of allergenicity were shown among the components in Rye, as compared with the Wheat and Barley homologues (7-8). IgE antibody studies have also shown a strong association between the levels of allergen-specific IgE to Wheat flour and those to Rye and Barley flour, and cross-reacting proteins could be demonstrated using competitive RAST inhibition studies (11). The existence of cross-reacting proteins between Barley, Rye and Wheat flour extracts, as well as among the pollens of cereals and cereal flours, has been reported (25).

The major Wheat allergen associated with exercise-induced anaphylaxis is an omega-5 gliadin, and similar allergens have been detected in Rye. The gamma-70 and gamma-35 secalins in Rye and the gamma-3 hordein in Barley were shown to cross-react with omega-5 gliadin, a major allergen in Wheat-dependent, exercise-induced anaphylaxis, suggesting that Rye and Barley may also elicit symptoms in patients with Wheat-dependent, exercise-induced anaphylaxis (3).

Allergy to Kiwi, Poppy seed, and/or Sesame seed often occurs in patients with a simultaneous sensitisation to nuts and flour. In a study characterising these cross-reactivities, the degree of cross-reactivity among Kiwi, Sesame seeds, Poppy seeds, Hazel nuts, and Rye grain was found to be very high in these patients. The existence of both cross-reacting and unique components was observed; however, the authors report that the cross-reacting and unique components could be different for different patients (26).

Papain has been reported to cross-react with Bromelain, Wheat flour, Rye flour, Grass pollen and Birch pollen (27).

In a Polish study investigating the relationship between hypersensitivity in 944 children to grass pollens and to Wheat, Rye and Soya, a very high correlation between hypersensitivity to grass and the presence of IgE antibodies to Wheat, Rye and Soya was found (28).

Clinical Experience

IgE-mediated reactions
Rye and Rye flour may commonly induce symptoms of food allergy in sensitised individuals, in particular in bakers. Symptoms may include asthma, rhinitis, sneezing and wheezing. Food allergy with gastrointestinal symptoms, including nausea, vomiting, gastric irritation, abdominal pain and diarrhoea, has been reported. Cutaneous symptoms may include pruritis, urticaria, dermatitis, atopic dermatitis and angioedema. Anaphylaxis or vascular collapse with exercise has been documented (29-33).

In a Polish study utilising SPT for food allergens in 270 pollen-allergic patients, the most prevalent allergens were found to be to nuts, Celery, Rye flour, Carrot, Strawberry, Pork and beans (28). Oral provocation tests have also shown the relevance of Rye as a food allergen. Allergen-specific IgE and histamine-release tests were employed to evaluate patients with immediate hypersensitivity. Patients with delayed hypersensitivity underwent patch or lymphocyte-proliferation tests (32). In an evaluation of sensitisation to cereal in 40 children, the most important allergen was Wheat, followed by Barley and Rye (34).

Anaphylaxis with exercise following the ingestion of Rye has been reported (31), as well as exercise-triggered recurrent anaphylaxis or urticaria as a result of allergy to gliadin (found in Wheat, Rye, Barley and Oats) (35). A study has suggested that Rye and Barley may also elicit symptoms in patients with Wheat-dependent, exercise-induced anaphylaxis (3).

Eosinophilic esophagitis (EE) is often associated with concomitant atopic diseases; in children with EE, for whom food allergens have been identified as causative factors, elemental and elimination diets result in an improvement or resolution of symptoms. However, among adults, most patients are sensitised to aeroallergens (most commonly to grass pollen and cereals), which may cross-react with plant-derived food allergens. Six adults with permanently active eosinophilic esophagitis, who were sensitised to grass pollen and the cereals Wheat and Rye, underwent a double-blind placebo-controlled food challenge and were kept on an elimination diet, avoiding Wheat and Rye for 6 weeks. However, the challenge tests with Wheat and Rye did not provoke any symptoms of eosinophilic esophagitis in any, and the elimination diet failed in reducing disease activity. One patient noted an improvement of symptoms, but endoscopic and histopathologic findings were unchanged (36).

Occupational allergy to Rye exposure may occur in animal feed and husbandry workers, bakers and other employees in bakeries, other food industry workers, and wood workers.

Baker's asthma is the most frequent occupational lung disease in Switzerland and West Germany. Cereal flours, and more rarely flour parasites, are implicated as the responsible allergens. In a study of 31 patients with Baker's asthma, approximately 74% and 61% were found to have IgE antibodies to Wheat and to Rye flour respectively (37). Other studies have reported similar findings: bakers with workplace-related respiratory symptoms showed sensitisation to Wheat flour (64%), Rye flour (52%), Soya bean flour (25%), and alpha-amylase (21%) (38). Asthma has been reported following exposure to cereal flour contained in animal formula feeds (39).

Rye and Rye flour may also cause occupational rhinitis and dermatitis, as reported in studies conducted on bakers and pastry cooks (40-42). Allergy to Rye flour has been reported in bakers (43-44). Occupational protein contact dermatitis may result from contact with Rye (45).

Two bakery workers with baker's asthma and rhinoconjunctivitis, caused mainly by exposure to Rye flour, were described. Specific inhalation challenge with Wheat flour did not elicit an asthmatic reaction; however, both patients showed an early asthmatic reaction to a Rye flour challenge (14). Similarly, a baker with asthma reported a workplace response to Rye flour but none to Wheat flour, despite co-reactivity to both Wheat and Rye antigens. SPT, IgE antibody determination and basophil stimulation tests were positive for both Wheat and Rye antigen, but quantitatively greater for Rye than for Wheat. Bronchial challenge elicited a much greater response to the Rye-Wheat flour mix used in the bakery than to 100% Wheat flour. The authors concluded that the greater clinical response to Rye than to Wheat may be immunologically mediated, but could have also been due to the physical characteristics of Rye flour, such as the larger dose of inhaled airborne particles or an irritative effect (46).

In a South African study of 517 supermarket bakery workers, a quarter (27%) of bakers had skin reactivity to cereal flours or additives, with the most common sensitisers being cereal flours such as Wheat and Rye (16%) and the least common being Alpha-amylase (3%). A higher proportion had elevated IgE antibody levels to Wheat (26%), Rye (24%) and Alpha-amylase (4%) (47). In individuals with baker's asthma, immediate asthmatic reactions may occur, or there may be dual reactions consisting of an immediate reaction followed by late reactions after some hours (48).

In a Korean study evaluating the IgE sensitisation rate and cross-reactivity in an agricultural setting, of 5,340 patients complaining of various allergic diseases and visiting a Korean allergy clinic, the sensitisation rate to Rye grain was 9.5%. Buckwheat and Soybean were the most prevalent allergens (49).

Cereal flours are used in the wood industry to improve the quality of the glues necessary to produce veneer panels. Three individuals were found to be allergic to cereal alpha-amylase inhibitors, which are important occupational allergens responsible for baker's asthma, and which are members of the alpha-amylase inhibitor family, allergenic proteins found in Rye, Barley and Wheat (50).

Occupational allergy to Rye flour was reported in 9 wood workers who were exposed to wood dust and experienced asthma and/or rhinoconjuncitivis. They worked as carpenters or sawmill operators. The adverse reactions appeared to be caused by the Rye flour used in the manufacture of agglomerate boards. SPT for a range of wood dust extracts was negative in 7 of the 9. One individual was shown to have positive SPT to Western red cedar and ramin, and another to Western red cedar and iroko. In contrast, all subjects were shown to have skin reactivity to Rye. (A commercial Rye flour extract was used both in the skin and in the conjunctival tests.) Five were positive on bronchial challenge tests (1).

Other reactions
Rye contains a gluten-complex protein which may result in coeliac disease (coeliac enteropathy) in genetically susceptible individuals. (51) Although the prevalence of coeliac disease is high in northern Europe, differences among countries exist. Among 771 children (381 Swedish and 390 Danish) investigated for suspected coeliac disease (CD), only 24 CD patients were found among the Danish children, compared with 155 in the Swedish group, despite the closely related ethnic, geographical, and cultural background of the two populations. The difference was attributed to a difference in the amount of gluten-containing Rye flour eaten. The Danish infant diet differed significantly from the Swedish one in containing a larger amount of the lower-gluten Rye flour (52).

Vasospasm related to ergot intoxication has been recognised since the Middle Ages, when it occurred due to ingestion of Rye contaminated with the mould Claviceps purpurea. Today ergotism is a rare cause of peripheral ischaemia, most often associated with ergotamine tartrate therapy for migraine headaches (53). Nevertheless, an awareness of this condition is important, as cases of ergotism may still occur. A 42-year-old farmer afflicted for 6 months with increasing pain in both feet and calves was reported. Angiography demonstrated progressive narrowing of all lower-leg arteries. There were no palpable pulses in the right foot, and those in the left foot were markedly reduced. The patient had been exposed by inhalation to ergotamine-containing milling dust in the preparation of Rye flour. A high plasma ergotamine level was documented. Chronic ergotamine inhalation can cause ergotism affecting peripheral arteries (54).

Compiled by Dr Harris Steinman, harris@zingsolutions.com


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