Vegan diet - alternative protein sources as potential allergy risk

One of the most important plant protein sources are cereals. With regard to wheat the allergologist has to consider different wheat-associated diseases, basically the IgE- and non-IgE-mediated entities.

IgE-mediated entities are wheat allergy including wheat-dependent exercise-induced anaphylaxis (WDEIA) and the occupational disease bakers' asthma. Presently, there are 29 wheat (28 Triticum aestivum and one Triticum turgidum ssp. durum [Durum wheat]) allergens documented in the WHO/IUIS database, of which 16 (15 Triticum aestivum and 1 Triticum turgidum ssp. durum) are associated with food allergy (Tab. 1; [4, 27]). The non-IgE-mediated entities consist of celiac disease and non-celiac wheat sensitivity.

A 65-year-old man who had experienced two anaphylactic reactions due to unknown causes with pruritus starting at the head with subsequent generalization, urticaria and drop of blood pressure presented in the Interdisciplinary Allergy Outpatient Clinic Lübeck/Borstel. During the described episode an adrenalin pen had been applied and development of further symptoms avoided.

So far, the history for type I allergy revealed an inhalant allergy to grass and rye pollen with seasonal rhinitis.

IgE-antibody detection was performed (Tab. 2).

Skin prick test (prick-to-prick test) revealed a reaction to wheat flour of 10 mm, which was stronger than that to the positive control histamine (7 mm).

A wheat-dependent exercise-induced anaphylaxis (WDEIA) could not reliably be diagnosed because the patient could not undergo an oral challenge accompanied by standardized exercise due to a heart disease. However, the facts that there were only two incidences and alpha-GAL syndrome could be excluded are highly suggestive for the effect of augmenting factors in addition to wheat consumption. At a follow-up visit 4 years later, he reported to be completely free of symptoms since avoidance of all wheat products. The peculiarity of this case is that it is an example for the value of molecular allergy diagnostics when patients are diagnosed with idiopathic anaphylaxis: The IgE-reaction to wheat extract was non-existent; however, when rTri a 19 was used, the strong skin test reaction to wheat flour was confirmed, and a reliable dietary recommendation could be given.

Soybean and products made thereof are an integral part of the vegan diet. Particularly birch pollen allergic individuals may react severely to soy milk, soy rice drinks, soy yoghurt, etc., based upon a pollen-associated food allergy for which the sequence and structural similarity between Bet v 1, the major allergen in birch pollen, and Gly m 4, the Bet v 1 homologue in soy are responsible [5]. In general, Bet v 1-associated food allergies present with mild to moderate symptoms, mostly with an oral allergy syndrome. However, this is often enough not the case with soy products: Here the reactions can be much more severe due to the amount of allergen consumed and the fact that the allergenic protein, normally destroyed by heat, had not been exposed to heat long enough during food processing (summarized in [3]). There are presently eight soybean allergens documented in the WHO/IUIS database (Tab. 3).

On the other hand, several consumers meanwhile try to substitute soy with lupine products (Fig. 1) because the latter is not genetically modified. Lupine serves as food as well as food additive. Lupine flour has favourable nutritional properties, it is gluten-free which makes it a valuable substitute for wheat in case of wheat allergy, and it is lactose-free. It is preferably used by vegetarians and in a vegan diet, and its consumption continues to increase! As an ingredient it is often used in wheat flour, however, there are lupine pasta, lupine sausages, lupine ice cream, lupine ketch up, etc. [6, 7]. Lupine allergy can be severe although it is not as potent as peanut [8]. It manifests itself as food allergy and, less often, as occupational disease (bakers' asthma with and without reaction to the ingestion of lupine containing food). Like soy, lupine has to be declared on ingredient lists [9]. The first description of a lupine allergy was in 1994, when a peanut allergic individual reacted severely to lupine pasta [10]. The potential to react to lupine via cross-reactivity to peanut should not be underestimated [8], because it makes lupine a "hidden allergen" for those who are not aware of the cross-reactivity. There is, however, a considerable number of lupine monosensitizations [6]. The first report on lupine allergy in Germany in 2006 was such a patient [11]. Only three allergens have so far been accepted and documented by the WHO/IUIS allergen nomenclature subcommittee: Lup an 1 (β-conglutin); Lup an 3 (lipid transfer protein), and Lup a 5 (profilin). Three different lupine species are dominant in foods: Lupinus albus (white lupine), Lupinus angustifolius (blue lupine), and Lupinus luteus (yellow lupine). One lupine species is not exactly like the other regarding the protein and allergen content and distribution [12]. A very recent study on cross-reactivity among legumes in 195 peanut-allergic children showed sensitization to lupine, fenugreek, soy and lentils in descending order [13].

Fenugreek (Trigonella foenum graecum of the Fabaceae family) also belongs to the legumes. It is consumed as dried and roasted seeds or as flour (Fig. 2), in the form of spices (e. g. curry), in cheese, baked goods, confectionery, and in coffee substitutes and herbal teas [14]. It serves as food and is an ingredient of traditional medicine as well. The first description as food allergen source dates back to 1997, when severe reactions after ingestion, inhalation and external application of fenugreek seed powder were published [15]. Anaphylaxis to fenugreek in curry spices has also become known since then [16, 17]. As has been observed for lupine, fenugreek induces not only food allergy and anaphylaxis but occupational asthma as well [18]. No single allergens of fenugreek have so far been accepted and documented by the WHO/IUIS allergen nomenclature subcommittee. A clinically most relevant aspect is that the data speak in favour of peanut being the primary sensitizer, as sensitization to fenugreek is mostly the result of a pre-existing peanut sensitization, and fenugreek monosensitization is very rarely observed [14].

Some vegetarian and vegan dishes contain several food allergen sources with high allergenic potential in parallel. A case report on an anaphylactic reaction to "falafel" demonstrates this impressively [19]: A 28-year-old woman developed an anaphylactic reaction grade III after ingestion of falafel. Generally, falafel consists of mashed beans and/or chickpeas plus garlic, herbs and spices. Sometimes, wheat or pea flour or soy is additionally used. Falafel may be served together with tahini sauce, which consists of sesame. Taken together, falafel may present a highly allergenic food [19]. Although the exact content of the anaphylaxis-causing falafel dish remained obscure in the cited case report, allergy diagnostic tests including oral food challenge revealed an immediate type allergy to pea. In addition, the presentation of several highly allergenic foods in one meal may cause a summation effect via single allergens with similar structures that are ingested at one certain time point, which in the end is responsible for the severity of the reaction [19].

So far, three allergens in pea (Pisum sativum) are listed in the WHO/IUIS database. There is evidence that the storage proteins Pis s 1 and Pis s 2 are the major pea allergens [20].

Like fenugreek pea does not have to be documented on ingredient lists. With regard to pea an increase in reactions can be expected as pea is used more and more in highly processed vegan foods [21]. Apart from peanut and soy, single allergens from other legumes are not yet available for routine allergy diagnostic tests.

Apart from storage proteins there are other protein families that are associated with severe allergic reactions. Those are lipophilic (oleosins) and lipid-associated proteins (LTP, lipid transfer proteins). Particularly oleosins that are present in oil seeds and most probably absent in aqueous extract-based allergy diagnostic test solutions have been described as being responsible for severe reactions after ingestion of peanuts, hazelnut, sesame, soy, sunflower, walnut, and recently buckwheat [22, 23], and some have already been well characterized and documented in the WHO/IUIS database ([4]; Table 4; [23]). A study on 76 peanut allergic patients in Borstel/Lübeck showed that those sensitized to oleosins suffered severe symptoms ([24], updated).

As mentioned above, we thought oleosins to be the cause of a severe reaction to sesame when a patient with a plausible history of an anaphylaxis after consumption of a bread roll with sesame was completely negative in routine allergy diagnostic tests. Total IgE: 11.6 IU/ml; serum tryptase 5.5 µg/L, specific IgE was negative to sesame extract, rSes i 1 (storage protein), apple extract, wheat extract, rTri a 19 (omega-5-gliadin), and marker allergens like rTri a 14 (LTP), rMal d 1 (Bet v 1-homologue), rMal d 3 (LTP). His serum was also IgE negative for peanut and lupine seed extracts, the latter being a common ingredient of wheat flour. The oral provocation was positive for sesame. In addition, our experimental investigation with whole sesame extract (obtained via acidic and alkaline extraction) revealed IgE-binding to sesame proteins - which based on their molecular weight were storage proteins - and to peanut oleosin-enriched extract of roasted sesame in immunoblot, which is also suggestive for an IgE-reaction to oleosins [25].