Allergen Description
Several antigenic constituents between 10 and 120 kDa have been revealed by immunoblotting studies (2-3). Sera of 11 patients were used to characterise allergens in Kiwi fruit, Latex, Avocado, and Banana and to identify cross-reactions among these allergen extracts. In Avocado extract, IgE-binding components of 27, 43, 52, 58, 65, 75, and 88 kDa were seen. Immunoblot inhibition demonstrated that almost all IgE-reactive bands in Latex, Avocado, and Banana extracts and 2 components of 43 and 67 kDa in Kiwi fruit shared common IgE epitopes (4).
The following allergens have been characterised:
- Pers a 1, a class 1 chitinase, also known as a hevein-like protein (5-12).
- Pers a 4, a profilin (13).
- Pers a hevein (11).
Pers a 1, the major Avocado allergen, is a class I chitinase. It is a 32 kDa heat-labile protein. In a study, Pers a 1 induced positive skin reactivity responses in 7 of 8 patients with Latex-fruit allergy (5,7-8); and in a another study, it was recognised by 15 out of 20 Avocado- and/or Latex-allergic patients (9).
Pers a 1, a class I chitinase, is the panallergen involved in Latex-fruit syndrome. This substance was shown to be extensively degraded when subjected to simulated gastric fluid digestion, but the resulting peptides, particularly those corresponding to the hevein-like domain, were clearly reactive both in vitro and in vivo (10).
Potential Cross Reactivity
An extensive cross-reactivity among the different individual species of the genus could be expected but has not been documented yet (14).
Natural rubber latex IgE-mediated hyper-sensitivity is probably among the greatest challenges in the treatment of allergies during recent years. Some Latex allergens cross-react with plant-derived food allergens, and this has been termed the “Latex-fruit syndrome” (15). Almost 50% of the Latex-sensitised children have food allergies, mostly to Banana, Kiwi and Avocado (16).
Avocado contains a class I chitinase, a defense-related plant protein, and this panallergen results in extensive cross-reactivity with foods from different food families, including Green bean (6,17-18). The class I chitinase cross-reacts with a major Latex allergen, hevein, and is responsible for the syndrome (19-21). Hevein (Hev b 6.02 and Hev b 6.01) has elsewhere been reported to be the major cross-reacting allergen with Avocado in subjects with Latex allergy (8, 22-23). Sequence comparison has shown that Pers a 1 and prohevein had 70% similarity in their chitin-binding domains (9). This was confirmed by a study of Banana, Avocado, and Chestnut, which demonstrated a 65-70% sequence identity with the Latex hevein (24). Highly related 25 kDa class II chitinases lack the hevein-like domain, and in Avocado no IgE-binding capacity was shown by these class II enzymes (25). Skin prick test reactivities against purified proteins were examined in 15 patients with Natural rubber latex allergy. Eleven (73%) patients had skin prick test reactions to isolated hevein-like domains of Avocado and Banana, but only 1 (7%) patient reacted to their corresponding 31 kDa endochitinases. A hevein-like domain from Avocado and one from Banana inhibited binding of IgE to prohevein (Hev b 6.01) in 59% and 38% of patients, respectively, whereas corresponding percentages for 31 kDa endochitinases were 17% and 20%, respectively. The study concluded that the isolated hevein-like domain molecules alone, but not when linked to endochitinases, seem to be responsible for IgE-mediated clinical reactions in Latex-fruit syndrome. Isolated hevein-like domains, but not 31 kDa endochitinases, are responsible for IgE-mediated in vitro and in vivo reactions in Latex-fruit syndrome (11).
Hevein has also been implicated in the cross-reactivity seen between Avocado, Custard apple and Aubergine. Purified Hev b 6.02 and Pers a 1 induced positive responses in skin prick tests (12).
The Hevea brasiliensis Latex chitinase, designated Hev b 11, displays 70% identity to the endochitinase from Avocado, and its hevein domain displays 58% identity to hevein (Hev b 6.02). A study concluded that Hev b 11, a class I chitinase, is another allergen from Hevea Latex with a chitin binding domain, but that it displays a different IgE binding capacity, compared with hevein (26). A recombinant Hev b 11.0102 class I chitinase from Natural rubber latex plant leaves was reported to represent an allergen of intermediate prevalence in NRL, and cross-reactivity with certain fruits was suggested (27).
Considerable immunologic cross-reactivity between Natural rubber latex and Avocado has been reported. In a study, sera from 18 patients with previously verified Latex allergy were used as the source of IgE antibodies, and 11 of the patients underwent SPT with fresh Avocado. Fourteen of the 18 sera (78%) had IgE antibodies that bound to a total of 17 Avocado proteins with apparent molecular weights ranging from 16 to 91 kDa. The 10 most strongly reacting sera were used for immunoblot inhibition studies. Binding of IgE antibodies to solid-phase Avocado proteins was inhibited in a dose-dependent manner: 100 micrograms of NRL proteins inhibited IgE binding to 15 of the 17 Avocado proteins, and 10 micrograms caused inhibition to 13 protein bands. Skin reactivity to fresh Avocado was detected in 7 of the 11 patients with Latex allergy. The study reported that the large number of inhibitable proteins in immunoblot experiments, and clinical observations from skin prick tests suggest considerable immunologic cross-reactivity between NRL and Avocado. The study concluded that the observed cross-reacting protein components may be responsible for the recently reported type I hypersensitivity reactions to NRL and Avocado in patients with a pre-existing allergy to either allergen (3).
In a French study of 243 children attending an allergy out-patient unit during 1 year, the prevalence of Latex allergy was 1.3%. Avocado allergy was the food allergy most commonly associated with clinical symptoms (28).
A number of studies have reported cross-reactivity between Latex and a variety of foods, including Chestnut, Banana, Avocado, Passion fruit, Celery, Potato, Tomato, Kiwi and Peach (29-34).
An increasing number of plant sources, such as Avocado, Banana, Chestnut, Kiwi, Peach, Tomato, Potato and Bell pepper, have been associated with the Latex-fruit syndrome (35). Although in Latex-allergic patients multiple sensitisation to fruits may be observed, Banana and Avocado are the substances most frequently involved, followed by Chestnut and Melon (59). In 3 patients who developed anaphylactic reactions to both Latex and food, the food items that led to anaphylactic reactions were, for each patient, Banana and Avocado; Banana, Avocado and Buckwheat; and Banana, Avocado and Tomato (36).
Cross-reactivity with fruit in Latex-allergic patients has to be taken into account in evaluating and counseling, as it will be relevant for 60 to 70% of these individuals (37). Cross-reactivity may not be equal among the foods implicated. For example, in a study of 47 Latex-allergic patients, immunological reactivity to foods was found in 33. Seventeen patients manifested a clinical allergy to at least 1 food, including 11 cases of anaphylaxis, and 14 cases of local sensitivity reactions. Positive food skin reactivity was detected most frequently with Avocado (53%), Potato (40%), Banana (38%), Tomato (28%), Chestnut (28%), and Kiwi (17%). Cross-reactivity to Potato in Latex-allergic patients may result from a broad class of plant proteins known as patatins (38).
Hev b 7 is a Hevea brasiliensis Latex allergen with sequence identities of 39% to 42% to patatins. However, Hev b 7, patatins, and their homologues do not contribute to cross-reactivity in Latex-fruit syndrome (39).
Other studies have reported similar findings. In a study of cross-reactivity among 13 Latex-allergic individuals also allergic to food, the most frequent food hypersensitivities were to Avocado (n=9), Chestnut (n=9), Banana (n=7), Kiwi (n=5) and Papaya (n=3) (40). Similarly, in a study investigating the prevalence of Natural rubber latex sensitisation and allergy in children with atopic dermatitis, 12 of the 74 atopic children studied had circulating IgE antibodies to Latex. Of the specific food IgE evaluations, 18.4% (93 out of 505) were positive, and 69.9% were observed in the group of children with Latex-specific IgE antibodies; the evaluations were most frequently positive to Potato, Tomato, Sweet pepper, and Avocado. Twenty children without proven Latex sensitisation showed increased food-specific IgE antibodies, most frequently to Potato, Banana, and Chestnut (41).
Similarly, in 82 patients (43 men and 39 women, aged between 18 and 45 years) with Latex allergy, 39 (47.5%) were found to have positive SPT to fruit. SPT with fruit extracts was positive in 28 patients (Kiwi [n=21], Banana [n=17], Avocado [n=8], Papaya [n=3]); the prick-by-prick test showed a lower number of positive results (Kiwi [n=7], Banana [n=4], and Avocado [n=3]) (42).
In 137 patients with Latex allergy (with food allergy having been diagnosed by a convincing history of possible IgE-mediated symptoms occurring within 60 minutes of ingestion), 49 potential allergic reactions to foods were identified in 29 (21.1%) patients. Foods responsible for these reactions included Banana (n=9; 18.3%), Avocado (n=8; 16.3%), shellfish (n=6; 12.2%), fish (n=4; 8.1%), Kiwi (n=6; 12.2%), Tomato (n=3; 6.1%), Watermelon, Peach, Carrot (n=2; 4.1% each), and Apple, Chestnut, Cherry, Coconut, Apricot, Strawberry, and loquat, (n=1; 2.0% each). Reactions to foods included local mouth irritation, angioedema, urticaria, asthma, nausea, vomiting, diarrhoea, rhinitis, and anaphylaxis (43).
In a Latex allergy study, positive food-specific IgE antibody tests occurred most frequently with Avocado (53%), Potato (40%), Banana (38%), Tomato (28%), Chestnut (28%), and Kiwi (17%) (38).
The majority of studies document cross-reactivity between Latex allergy and Avocado, 1 among a number of cross-reactive foods, but not often between Avocado and other food. Nonetheless, these studies indicate that an Avocado-allergic individual is at risk of being allergic to a number of these foods because of the presence of the class I chitinase. Illustrating this, in a study of 17 serum samples from patients with well-documented Latex allergy, 10 demonstrated an allergy to Avocado, sometimes associated with Banana (2). In a study examining Banana allergy in 4 patients who were Banana-allergic, 1 patient also had a sensitisation to Avocado, but not to Latex or pollen (44).
However, Latex-allergic individuals may demonstrate IgE antibodies to these cross-reactive foods without clinical significance. For example, in a report of 2 children with Latex allergy, skin reactivity was detected for Banana, Kiwi, Pineapple, Apricot, Avocado, and Grape, but these children presented no symptoms after ingestion of these fruits (45). This finding is supported by a number of other studies. In a study of 136 patients with well-documented, clinically relevant, immediate-type hypersensitivity against Latex proteins, serum samples were analysed for IgE antibodies against a panel of different fruits. Cross-reacting IgE antibodies recognising Latex and fruit allergens (Papaya, Avocado, Banana, Chestnut, Passion fruit, Fig, Melon, Mango, Kiwi, Pineapple, Peach, and Tomato) were demonstrated by RAST-inhibition tests. Of the patients, 42.5% reported allergic symptoms after ingestion of these fruits, and a total of 112 intolerance reactions were recorded. However, fruit-specific IgE antibodies were detected in serum samples from only 32.1% of the patients who perceived symptoms due to these fruits. Therefore, serologic tests seem to be of low efficacy for prediction of food allergy in Latex-allergic patients (46). In 2 atopic Latex allergy patients with skin reactivity and IgE antibodies to Avocado and other fruit, no clinical symptoms occurred (47).
Cha o 2, a major allergen of Japanese cypress (Chamaecyparis obtuse) pollen, displays a high homology (a 74.3% identity) with Cry j 2, a major allergen of Japanese cedar (Cryptomeria japonica) pollen. This allergen is a polygalacturonase and showed a significant identity with a similar protein isolated in Avocado, Tomato, and Maize, as well as Cry j 2 (48). The deduced amino acid sequence of cloned Cry j II showed significant identities to those of the polygalacturonases associated with fruit ripening in Tomato (40%) and Avocado (43%) and also found in pollen of Maize (34%) (49). The allergenic potential of the Avocado-equivalent protein was not examined.
Allergy to other foods has been associated with Kiwi allergy: among Kiwi-allergic patients, there were strong reactions to Apple and Hazelnut; and moderate reactions to Carrot, Potato, and Avocado. A proposed mechanism was not suggested (50). Similarly, cross-reactivity among Apricot, Avocado, Banana, Cherry, Chestnut, Grape, Kiwi, Papaya, Passion fruit, Peach and Pineapple was reported (51).
In a study of 5 patients with oral allergy syndrome or anaphylaxis after the ingestion of Fig, and 1 patient with symptoms from exposure to Ficus benjamina trees (Weeping Fig), skin reactivity was demonstrated most often to Kiwi fruit, Papaya, and Avocado.
Sensitisation to Rubber latex could not be demonstrated in any of the patients. The study concluded that allergic reactions to fresh or dried Fig can present as a consequence of primary sensitisation to airborne Ficus benjamina allergens independent of sensitization to Rubber Latex allergens. Kiwi fruit, Papaya, and Avocado as well as Pineapple and Banana may be other fruits associated with sensitisation to Ficus allergens (52).
Among 4 patients with an allergy to Ficus benjamina, the 2 plant growers showed a cross-allergy to other Ficus species. Two patients had a cross-allergy to Latex and the associated cluster of tropical fruit (Banana, Kiwi, Avocado, and Chestnut) (53).
In a study that reported a sensitisation prevalence of 2.5% to Ficus benjamina Latex that occurred mostly independently of Latex allergy, sensitisation to F. benjamina was specifically associated with positive skin tests to fresh Fig (83%), dried Fig (37%), Kiwi fruit (28%), Papaya (22%), Avocado (19%), Banana (15%), and Pineapple (10%) (n = 54). The authors suggested that the cross-reactivity was mediated at least in part by the thiolproteases ficin and Papain (54).
In a study investigating the prevalence of Avocado allergy, 8 of 21 Avocado SPT positive patients reported that symptoms repeatedly followed the ingestion of Avocado; 7 also reported oral symptoms following Cantaloupe ingestion (55).
