• cereals;
  • fruits;
  • legumes;
  • lipid transfer proteins;
  • pathogenesis-related proteins;
  • plant-origin food allergens;
  • seeds;
  • seed storage proteins


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

Plant-origin foods, especially nuts and seeds, are the most important sources of food allergic reactions. An important characteristic is the quantitative and qualitative variability of their content in allergenic molecules, depending on plant growth, ripening, environmental stresses or industrial processing. In this review we will focus on newly identified allergens. Recent research have characterized and extensively studied their biochemistry, structure and immunological properties.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

Plant-origin foods can be considered the most important sources of food allergic reactions, especially in adults. Recent epidemiological studies (1–3) showed that they are the most frequent cause of systemic allergic reactions and of fatal anaphylaxis. Nuts and seeds, particularly peanut, are most commonly involved, but fresh fruits and vegetables are also described as causes of allergic symptoms of variable severity (4).

Important allergenic aspects of plant-origin foods are the clinically not yet well defined cross-reactivity, and the quantitative and qualitative variability of the content in allergenic molecules.

Regarding the first point, many plant-origin foods bare from closely related botanical families and have structurally homologous proteins, but they are not all equally allergenic, thus making it difficult to distinguish in vitro and in vivo cross-reactivity. This is still a debated point in establishing the risk of cross-reactions in patients allergic to a specific food and in deciding the details of an elimination diet.

Regarding the second aspect, variability in the amount of allergenic proteins is quite common, as most plant allergens are either ‘pathogenesis related proteins’ or ‘seed storage proteins’, so their expression in the plant can vary depending on the phases of growth, ripening, exposure to pathogens or environmental stresses. Qualitative differences in the allergenic content can be caused by processing, which can destroy allergenic epitopes or create new allergens normally not found in the natural food.

In view of the special features of plant-origin food allergens, careful study of their biochemistry, structure and immunological properties is necessary. In this review we will focus on newly identified allergens, that have been characterized and extensively studied in recent research.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

One of the most dangerous allergenic foods is peanut (Arachis hypogea), a nut belonging to the family of legumes. The major peanut allergens Ara h 1, Ara h 2 and Ara h 3, corresponding to a vicilin, a conglutin and a glycinin, respectively, were identified by Burks et al. (5–8) using sera from children with atopic dermatitis who reacted to peanut in a double-blind placebo-controlled food challenge (DBPCFC). At present, these are the only peanut allergens with demonstrated clinical relevance. Kleber-Janke et al. (9), using a phage display technology, described other allergens named Ara h 4, Ara h 5, Ara h 6 and Ara h 7, which correspond to a glycinin, a profilin, and two different conglutins, respectively, but their clinical importance is not yet clear. Becker et al. (10) calculated the prevalence of sensitization to every single allergen in a population of 40 patients sensitized to peanut. Besides the already known Ara h 1 (prevalence 65%) and Ara h 2 (85%), Ara h 4 (53%) was also a major allergen. Ara h 3 was not investigated, being an isoform of Ara h 4, with 91% identity, while Ara h 5 (13%), Ara h 6 (38%) and Ara h 7 (43%) were minor allergens. The authors found that sensitization to Ara h 6 was associated with more severe clinical symptoms.

Since peanuts are usually consumed as roasted nuts, it is important to assess their allergenic potential after thermal procedures. Maleki et al. (11) performed an in vitro study with raw and roasted peanut extract and with purified Ara h 1 and Ara h 2, and found that roasted peanut bound serum IgE from allergic individuals at levels about 90-times higher than raw peanut. Roasted peanut was also more resistant to degradation by endogenous proteases and to gastric digestion. This was probably because of the structural modifications of the proteins which, heated in the presence of sugars, undergo the Maillard reaction with formation of protein cross-links, loss or modification of amino acids and other noncross-linking changes. It has also been demonstrated that Ara h 1 is cross-linked through the Maillard reaction to form covalently associated trimers and hexamers, which can bind IgE antibodies, so this reaction seems to create novel IgE-binding sites and consequently new allergens.

A common problem in peanut allergic patients is whether the elimination diet should also exclude other legumes, for example soy (12). In vitro IgE cross-reactivity between peanut and soy allergens is quite frequent, but clinical cross-reactivity seems uncommon, as only 6.5% of peanut allergic patients mildly reacts also to soy (13). Nevertheless, a recent study by Foucard and Malmheden Yman (14) showed that soy allergy is an underestimated cause of severe anaphylactic reactions. They reported, from 1993 to 1996, 12 cases of life-threatening reactions to different foods, six due to soy, and four fatal cases of anaphylaxis, probably due to soy, in asthmatic peanut allergic patients with no previously known allergy to soy. This study suggests that, in some subjects, sensitization to peanut may provoke severe reactions also to apparently inoffensive foods belonging to the same botanical family.

The cross-reactivity at molecular level between peanut and soy has been investigated but the allergens involved have not yet been identified.

Spanish authors (15) have studied another legume, the chick pea (Cicer arietinum), whose IgE binding properties were not affected by boiling, indicating that the majority of chick pea allergens were thermostable. The recognized major allergens of 20 kDa and 21.8–69.8 kDa were not characterized. This is the only study of the allergens of this legume, which was recently reported as a cause of fatal anaphylaxis (3).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

Seeds are an important cause of allergy, and can provoke severe even though not frequent reactions. The first allergens described in seeds were from yellow mustard (Sinapis alba), Sin a 1 (16), from oriental mustard (Brassica juncea), Bra j 1 (17), and from castor bean (Ricinus communis), Ric c 1 (18). All these allergens belong to the 2S albumin group (Table 1).

Table 1.  2S albumins
AllergenSourceBotanical nameM.W. (kDa)Isoelectric point
Ric c 1Castor beanRicinus communis11–127.0, 11.1
Sin a 1Yellow mustardSinapis alba14.610.0, 12.2
Bra j 1Oriental mustardBrassica juncea16–16.410.4, 12.5
Jug r 1English walnutJuglans regia15–16
Ber e 1Brazil nutBertholletia excelsa99.0–10.0
Ses i 1Sesame seedSesamum indicum106.0, 6.5, 7.3

We have also identified the major allergen of sesame seeds (Sesamum indicum), named Ses I 1, as a 2S albumin (19). Sesame is an emerging cause of food anaphylaxis, due to the increasing use of the seeds in food products, some of them for infants, thus explaining the finding of sesame allergy even in extremely young children (20). Our study comprised 10 patients, seven children and three adults, with severe IgE-mediated systemic reactions to sesame seeds: we found no significant differences in the IgE binding profile of adults and children, as all the patients strongly reacted to a 10-kDa 2S albumin. This allergen was highly homologous to other allergenic proteins like the 2S albumins of Brazil nuts (similarity 87%, identity 47%), castor beans (similarity 65%, identity 41%), and sunflowers (similarity 93%, identity 43%); however, cross-reactivity between these allergens has not been studied.

Another allergenic 2S albumin has been described in the seeds of sunflower (Helianthus annuus), using sera of five sunflower seed allergic patients (21, 22). The allergenic potential of this protein is particularly important, because it has already been employed in the production of transgenic crops, such as alfalfa and lupin for use in animal feed, in order to enhance their nutritional value, as it is rich in sulphur-containing amino acids. In particular, it is necessary to investigate its cross-allergenicity with the major allergen of Brazil nut (23), a 2S albumin which was transferred to soy by genetic engineering, also transferring its IgE binding capacity (24).


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

Cereals are the main alimentary source in the world; they can elicit both respiratory allergic reactions and food allergic reactions after ingestion. Until recently, the most important cereal allergen identified was the α-amylase/trypsin inhibitor, which can sensitize by both the inhalative and the gastrointestinal routes: it has been described as the major allergen in baker's asthma and also in atopic children with positive DBPCFC to wheat (25) and in rice allergic patients (26).

Recent studies led to the identification of new food allergens in cereals: for example gliadin, which is an antigenic protein of wheat responsible for celiac disease, was also identified as the major allergen in wheat-dependent, exercise-induced anaphylaxis (27). In one study (28), 18 patients suffering from allergic reactions after ingestion of cereals followed by exercise, showed an IgE binding to a 65-kDa ω-5 gliadin in immunoblotting; 91% of these patients, in ELISA experiments, showed IgE antibodies also to γ-70 secalin of rye and to γ-3 hordein of barley. These allergens were thus cross-reactive with wheat ω-5 gliadin at IgE level, even if IgE antibodies showed greater affinity for the wheat allergen, which can be considered the primary sensitizer.

Varjonen et al. (29) underlined the importance of gliadin as an indicator of wheat allergy in atopic dermatitis (AD): they found a good correlation between positive skin prick test to gliadin and positive wheat open challenge in a population of 18 children with AD.

The first allergenic 2S albumin ever described in cereals was found in buckwheat (Fagopyrum esculentum), a cereal belonging to the Polygonaceae family, frequently used as a substitute for common cereals, especially in Asia, where it was described as a cause of severe respiratory and food allergy. In a clinical study (30) involving both allergic (showing symptoms after ingestion of buckwheat) and sensitized (without symptoms to buckwheat, but positive RAST) patients, several allergens were identified at different molecular weights, ranging from 9 to 67 kDa. Three of them were characterized and sequenced: the 9 kDa allergen, identical to the buckwheat trypsin inhibitor; the 16 kDa allergen, homologous to the α-amylase/trypsin inhibitor of millet; the 19 kDa allergen, homologous to the α-globulin of rice, one of the 2S albumins. The last was the only one specifically recognized more by buckwheat allergic individuals (78%) than by the sensitized ones (7%). No immunological cross-reactivity was seen between this allergen and the two recombinant 2S albumins Bra j 1 and Sin a 1.

Another recently identified cereal allergen is the major allergen of maize, a 9-kDa protein which belongs to the lipid transfer protein (LTP) family (31). These proteins are widespread in plants, where they play an important role in defence against pathogens and environmental stresses (32). The 22 selected maize-allergic patients experienced predominantly systemic, even life-threatening, reactions after ingestion of maize; symptoms localized only to the oral mucosa were rare. It is interesting to notice that maize LTP shares about 63% homology with peach LTP and rice LTP (79%), but lower homology with the LTPs of other cereals like wheat (59%) and barley (57%). This might explain the clinical reports of frequent allergic reactions to peach and rice and of tolerance to oral intake of wheat (bread and pasta) in maize sensitized patients.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References

LTP also act as major allergens in Prunoideae fruits, namely peaches, cherries, apricots and plums. In a previous study we found that all these fruits shared a cross-reacting low molecular weight allergen (33), characterized for the first time in peach as a basic protein belonging to the LTP family.

In a further study we identified the major allergen from apricot in a population of 30 patients with oral allergy syndrome (OAS), and showed it was an LTP with 95% sequence homology with peach (34). Besides this allergenic LTP, we found another LTP in apricot, similar to the first but not capable of binding IgE antibodies from allergic subjects, which was homologous with the Arabidopsis thaliana LTP: the role of this protein is still not clear (35).

We have also identified an LTP acting as a major allergen in plum, Pru d 3 (36), which shows more than 90% sequence homology with LTPs from peach and apricot. The high homology between these proteins accounts for the frequent clinical cross-reactivity between Prunoideae fruits observed in patients' histories (Table 2).

Table 2.  LTPs
Allergen nameSourceBotanical name
  1. All the allergenic proteins of this family up to now identified have a molecular weight of 9 kDa and an isoelectric point > 9

Zea m 14MaizeZea mays
Mal d 3AppleMalus domestica
Pru p 3PeachPrunus persica
Pru ar 3ApricotPrunus armeniaca
Pru av 3CherryPrunus avium
Pru d 3PlumPrunus domestica

The sensitization to Prunoideae fruits seems to involve different allergens in different populations. Scheurer et al. (37) evaluated 101 German cherry and birch allergic patients and seven Italian patients allergic only to cherry; the major sensitizing allergen of cherry in German patients was Pru av 1, homologous to Bet v 1 of birch, while the LTP allergen was recognized only by three patients. In Italian patients, however, LTP was the major allergen recognized by 100% of the patients. This study indicated that sensitization to a specific allergen may depend on genetic factors, so the allergenic profile of each food source must be defined in the different countries.

Sensitization to the widespread pathogenesis-related proteins of plants can cause unexpected cross-reactions between foods that are botanically unrelated, as in the case of maize–peach allergy in individuals sensitized to LTPs; another well-known example is the latex–fruit syndrome, which is due to the presence of cross-reacting molecules in latex (Hevea Braziliensis) and in avocado, banana and chestnut. Many latex allergic patients, in fact, also show IgE binding to these fruits. The main allergens responsible for this cosensitization are class I chitinases, proteins involved in the defence of the plant, which possess an N-terminal hevein-like domain homologous to the major latex allergen Hev b 6.02 (38). Sanchez-Monge et al. demonstrated that these allergenic proteins are induced by ethylene, a plant hormone used to accelerate fruit ripening, and destroyed by heat (39). These findings confirm that industrial treatments can affect the allergenic content of the finished products, and may explain why some plant foods that contain the class I chitinases, but are always cooked before eating, like the green bean (Phaseolus vulgaris), are not usually associated with the latex–fruit syndrome.

In conclusion, in the last few years an increasing number of studies have helped clarify some important aspects of allergy to plant-origin foods. New allergens have been described, some of them belonging to well-known families of allergenic proteins such as seed storage proteins, enzyme inhibitors, LTP and chitinases, and some belonging to families that were not previously known to be allergenic, like prolamines of cereals (gliadin and related proteins). Another important finding is that sensitization to a particular class of proteins often influence the clinical response, determining the quality or the severity of the symptoms, and also causing typical cross-reactions between different foods or between foods and aeroallergens. Moreover, recent studies suggest that the identification of many processes which the foods, and therefore the allergenic proteins that they contain, undergo, is important as regards the allergenic potential of each food source, because existing allergens may be destroyed or new allergens created by these procedures, thus affecting the allergenicity of the whole food source. So it is always necessary to investigate the structural and biochemical characteristics of the newly identified allergens, in order to establish if and how they can influence the allergenic properties of the proteins.


  1. Top of page
  2. Abstract
  3. Introduction
  4. Legumes
  5. Seeds
  6. Cereals
  7. Fruits
  8. References
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