Allergenic Sensitisation Mediated by Wolfberry

Classification of plant food allergens



Biological function

Common allergens


2S albumins

Seed storage

Wheat, peanut (Ara h 2, Ara h 6, Ara h 7), walnut (Jug r 1)


Defensin related

Peach (Pru p 3), hazelnut (Cor a 8), tomato (Lyc e 3), apple (Mal d 3), goji berries (Lyc bar 3)

α-Amylase/trypsin inhibitors

Protection against degradation and pathogens

Wheat (Hor v 1)


7S albumins (vicilin)

Seed storage

Buckwheat (Fag e 3), peanut (Ara h 1)

11S albumins (legumin)

Seed storage

Peanut (Ara h 3)

Structural proteins

Peanut (Ara h 5), hazelnut (Cor a 2), apple (Mal d 4), wheat (Tri a 12)

Homologous to Bet v 1
Pathogenesis related proteins (PR-10)

Carrot (Dau c 1)

The prolamin superfamily comprises the largest number of allergens. Three families of allergens are included within the prolamin superfamily: non-specific lipid transfer proteins (nsLTP), typically found in fruits and vegetables; seed storage albumins, found in seeds and nuts; and amylase/trypsin inhibitors, present in cereals. As a result of their biochemical composition, they are all resistant to digestion and thermal denaturation, which gives them high-potential allergenicity.

The other two most important superfamilies are cupins and profilins. The cupin superfamily comprises heat stable and highly allergenic allergens. The majority are storage proteins present in nuts. The profilins constitute a very conservative family of proteins, which confers them a high degree of cross-reactivity among different species. Profilins are responsible for tree pollinosis-associated food syndrome. Finally, the superfamily of the allergens homologous to Bet v 1 is the fourth superfamily. The food allergic reactions are primarily explained by IgE antibodies to Bet v 1, which cross-react with Bet v 1 homologous proteins. These allergens are mainly localized in the pulp of the fruit. Heat treatment of these foods destroys the native three-dimensional molecular structure but does not affect linear peptides, important for the late phase cellular reaction.

12.4 Cross-Reactivity

The term cross-reactivity is associated with the allergic clinical symptoms that individuals may experience after the consumption of/contact with some types of foods or pollens, even though they may have never previously been in contact with them. In contrast, the term co-sensitisation means the actual sensitisation to different allergenic sources with the production of specific antibodies to each of them.

From an allergenic point of view, cross-reactivity can be defined as the capacity of allergic individuals to react against allergenic sources to which they are not sensitised because they have not been exposed to them or have not developed specific antibodies against them. In this case, the components of the immunological system of patients (specific IgE) recognise the allergenic components (allergens) present in the offending food but with the particularity that these allergens are recognised only as a consequence of structural similarities with the allergen to which patients are actually sensitised. This recognition can occur due to the presence of common proteins/allergens in different organisms, known as panallergens, or as a consequence of similarities in specific regions of the proteins.

The term panallergen is used to define proteins/allergens that are widely distributed in different organisms, that have a common biological function and that share a somewhat common structure. nsLTPs and profilins are the most studied group of panallergens. Both are present in all plant kingdom organisms and are responsible for a large number of sensitisations, either by co-sensitisation or cross-reactivity.

The cross-reactivity between profilins from different organisms has been well established (Radauer et al. 2006). However, cross-reactivity between LTPs remains unclear. In a recently published study, the authors demonstrated that, although all LTPs have the same biological function, amino acid sequence varies significantly among organisms (Morales et al. 2014). Immunological studies performed with serum samples from animals and human patients demonstrated only partial cross-reactivity and suggested that, not only the proteins, but also the matrix in which proteins are contained could play a role in allergic symptoms (Schulten et al. 2011) because of its ability to act as an adjuvant for immune response. In this sense, authors suggested that allergic reactions could be related to primary sensitisation and not only to cross-reactivity.

Recognition as a consequence of similarities in specific regions of the proteins is less common and is mediated by proteins which share specific similar structures that can be recognised by common antibodies. This is the typical case of cross-reactivity known as “Bet v 1 Family”. In these patients, primary sensitisation seems to be produced by inhaling pollen proteins. Individuals experience symptoms when they ingest Bet v 1 homologous allergens such as carrots or apples (Bohle 2007).

12.5 Prevalence of Food Allergy

Food allergy appears to be a major and increasing problem, especially in Western countries. A dramatic increase in the number of affected populations has been observed in the last 20 years and the percentage of patients with some allergic symptoms increases year-on-year.

In recent years, globalisation, population interest in new flavours, rapid transportation and improvement of food preservation conditions have enabled new foods and flavours to spread throughout the world. Diet diversification and increasing demand for better quality and labour-saving products have increased the imports of high-value and processed food products in developed countries. As a result, individuals experience new and greater access to new allergenic sources to which they had never before been exposed. This may modify the sensitisation pattern of individuals, either because of new allergenic sensitisation provoked by the allergenic capacity of new foods, or individuals may react to the new food by cross-reactivity. The addition of kiwi to the Western diet at the end of the 1970s is a clear example of new sensitisation. Nowadays, kiwi is recognised as a potent allergenic source, and actinidin, one of its major allergens, was previously not habitually consumed in the Western diet. Moreover, goji berries are an example of sensitisation to new allergenic sources by cross-reactivity, in this case mediated by LTPs.

There is no clear consensus regarding the prevalence of food allergy in the general population, although different studies concur that there is a higher prevalence in children. In general terms, it has been estimated that 2 % of the adult population and 6–8 % of children suffer from food allergy. Although there is no clear consensus, the prevalence is probably underestimated because of a considerable under-diagnosed population. Moreover, these values are highly variable according to country. Western countries probably have the highest rates of food allergy. According to the European Academy of Allergy and Clinical Immunology (EAACI) guidelines (Muraro et al. 2014a; Nwaru et al. 2014), more than 17 million individuals suffer from food allergies in Europe. Food sensitisation, understood as patients with specific IgE but with no clinical symptoms, may double or triple this figure.

Double-blind, placebo-controlled food challenge (DBPCFC) is recognised as the most effective tool for allergy diagnosis. However, this diagnostic method has its flaws and is not always a routine practice mainly for methodological reasons. Therefore, actual prevalence of food allergy cannot currently be confirmed in the general population and further studies are required.

Factors such as age, sex, race, country of origin and residence, family or personal history of atopy or other concomitant allergic diseases play an important role in the development of food allergies. All these factors, as well as food consuming habits, may affect the prevalence of food allergy in different populations and explain different prevalence rates or sensitisation to different food allergens among patients living in different areas.

12.6 Clinical Management

Food allergy is associated with psychological distress in patients, especially in children, adolescents and their parents. It also causes anxiety and depression (Knibb and Semper 2013; Bacal 2013) in families as a result of the risk associated with this pathology (Muraro et al. 2014b). Undoubtedly, the most life-threatening effect of food allergy is anaphylaxis, understood to be a generalised or systemic hypersensitivity reaction mediated by the ingestion of food allergens which, on occasions, may be fatal for patients. In the last few years, the number of episodes of anaphylaxis induced by the food ingestion has increased dramatically, especially in developed countries. Anaphylaxis treatment guidelines recommend that at-risk patients carry adrenaline auto-injectors with them at all times (Song et al. 2014).

Pharmacological treatment is useful only for the symptomatic treatment of acute symptoms. Its use is recommended to alleviate mild-to-moderate symptoms and, until now, adrenaline is the only effective treatment for life-threatening episodes (Arnold et al. 2011).

Until now, dietary avoidance has been recognised as the only effective treatment for food allergy. However, long-term avoidance has to be carefully monitored because it can result in nutritional problems and affects patient quality of life.

Specific immunotherapy with food allergens is currently being investigated, although it is not yet suitable for routine practice. The capacity of this kind of immunotherapy to restore permanent tolerance to food has not yet been conclusively demonstrated. Three different approaches are under study, including subcutaneous immunotherapy, sublingual immunotherapy and induction of oral tolerance, also called oral desensitisation. Preliminary results obtained with subcutaneous immunotherapy suggest that this could be an effective alternative. Other studies with sublingual immunotherapy were associated with improved tolerance and the reduction of symptoms (Nowak-Wegrzyn and Albin 2014). Oral desensitisation is also one of the most frequently studied alternatives. Published results showed efficacy on many occasions, but there is no consensus regarding treatment, dose, allergens, time of exposure, long-term studies, etc. (Pajno et al. 2014).

12.7 Goji Berries Consumption-Mediated Allergy

Goji berries, considered both a fruit and a herb, have been part of the common diet in some Asian regions, such as China, Tibet and Mongolia, for more than 3000 years. In some of these countries, they are considered to be a true treasure and their properties almost have a mystical value. They are consumed daily even at high doses sometimes as a medicinal herb to treat diseases due to their healthy properties, or other times in search of “the source of eternal youth”, as part of the normal diet. However, to date no well-documented data related to sensitisation or allergic reactions have been reported by countries that were the first consumers, although, urticaria and rashes after goji berries’ ingestion has been described.

In Europe, according to the European Union Novel Food Regulation (http://​ec.​europa.​eu/​food/​food/​biotechnology/​novelfood/​index_​en.​htm), a food is judged to be novel if it has not been consumed in significant quantities in Europe prior to May 1997. When the consumption of goji berries started to spread throughout European countries, regulatory agencies investigated their previous consumption. Initially, authorities did not find a history of significant consumption of goji berries in Europe before 1997. However, in 2007, the UK Food Standards Agency determined that, in fact, there was a history of significant consumption of the fruit in Europe before 1997, and goji berries were removed from the Novel Foods list.

In the USA and Canada, farmers began cultivating goji berries during the first decade of the twenty-first century on a commercial scale.

Goji berries can therefore be considered as a food recently introduced into the European and North American diet. No cases of allergic reactions had been reported in the scientific literature until recently. Additionally, some occasional reactions such as urticaria-like or papular rashes have been linked to goji berry consumption and published in Chinese medicine textbooks, although they cannot necessarily be classified as allergic reactions (Bensky et al. 2004). Since 1990, more than 3000 adverse reactions have been described in China with more than 210 involving herbs.

The first two cases of anaphylaxis following the ingestion of goji berries that were investigated in depth on a worldwide scale were reported in Spain in 2011, and five additional cases were also reported in Spain in 2012. The consumption of goji berries was the common factor in each case, but the severity of symptoms, origin of patients and concomitant allergies differed. All of them were associated with preliminary sensitisation to LTPs. Table 12.2 details the eight clinical cases described in the literature.

Table 12.2
Clinical characteristics of all goji berries allergic patients published in the literature

Clinical cases with goji berry allergy




Specific IgE


Concomitant sensitisation associated to goji berries

Monzon et al. (2011)

27-year-old woman

Grade II anaphylaxis. Acute generalised urticaria, lip oedema, dyspnoea and acute rhinitis


Food: peach, tomato, green pepper

Panallergens: LTP

13-year-old girl

Generalised urticaria, severe pruritus and skin lesions (hives), angioedema and dysphagia


Food: peach, kiwi, almond, peanut, hazelnut, chestnut, rice, tomato

Panallergens: LTP

Pollens: Chenopodium album, Ambrosia

elatior, Platanus hybrida, Cupressus arizonica

Larramendi et al. (2012)

40-year-old man

Facial angioedema with dyspnoea


Food: peach

31-year-old man

Pharyngeal itching


Food: peach

Panallergens: LTP

30-year-old woman

Labial angioedema and perioral skin rash


Food: peach

Panallergens: LTP

36-year-old man

Itching in the mouth, ears and axilla


Food: peach

Panallergens: LTP

42-year-old woman

Severe generalised itching


Panallergens: polcalcin

Carnés et al. (2013)

65-year-old man

Oral allergy syndrome

No determined

Mono-sensitised to goji berries

21-year-old woman

Occasional urticarial and oral allergy syndrome


Food: tomato

Panallergens: LTP

43-year-old woman

Oral allergy syndrome and diarrhoea

No determined

Mites and cockroach

Gámez et al. (2013)

40-year-old woman

Immediate pharyngeal pruritus

No determined

Foods: fruits, king prawn, nuts, lettuce, escarole and soy

Pollens: grasses

IgE immunoglobulin E, LTP lipid transfer protein

The first case was a 27-year-old woman who developed grade II anaphylaxis 1 h after goji berry consumption, accompanied by acute generalised urticaria on the hands, palms and soles, lip oedema, dyspnoea and acute rhinitis, and required treatment with adrenaline. The second case was a 13-year-old girl who presented with generalised urticaria, severe pruritus and skin lesions (hives), angioedema and dysphagia after goji berry consumption.

In 2012, five new cases were reported. In this case, patients showed different severity and manifestations following goji berry consumption. The first patient was a 40-year-old man who complained of facial angioedema with dyspnoea (requiring epinephrine) while eating goji berries for the first time (30–40 berries). The second case was a 31-year-old man who reported pharyngeal itching lasting 30–60 min on 10–12 occasions, immediately after eating 10–15 goji berries and with symptoms increasing in intensity after each exposure. The third case was a 30-year-old woman who reported labial angioedema and perioral skin rash immediately after eating a new pack of 20 goji berries. The patient had previously tolerated a whole pack of goji berries. The fourth case was a 36-year-old man with a history of allergic rhinoconjunctivitis and urticaria due to peanuts who reported itching in the mouth, ears and axilla lasting 10 min immediately after eating a single goji berry. Finally, the fifth case was a 42-year-old woman who reported a 2-month history of severe generalised itching that resolved after avoiding goji berries. She was consuming approximately 20–30 goji berries daily for several months.

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Jun 28, 2017 | Posted by in PHARMACY | Comments Off on Allergenic Sensitisation Mediated by Wolfberry

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