Oral Allergy Syndrome – What ’ S New ?

Oral allergy syndrome/pollen-food syndrome (OAS/ PFS) affects up to 70% of patients with birch-pollen allergy. Prevalence is likely to continue to increase as the prevalence of inhalant allergies rises. Homologous proteins in fruits, vegetables, and pollens of grasses, trees and weeds are responsible for PFS. Component-resolved diagnosis (CRD) with recombinant allergens may assist with the diagnosis of this condition in the future. As there is currently no proven therapy for this syndrome, cooking and avoidance of offending fruits and vegetables are the only options. Correspondence: Dr Harris Steinman, Food & Allergy Consulting Services, PO Box 565, Milnerton 7435. E-mail [email protected] broad range of pollens and foods, including trees, grasses and weeds. Sensitisation to profilin occurs in approximately 20% of pollen-allergic patients, and patients sensitised to pollen profilins react to a broad range of inhalant and food allergens. An example is the birch pollen allergen Bet v 2. Patients who are sensitised to Bet v 2 often have symptoms upon ingesting apple, pear, carrot, and celery. Patients with allergies to grass pollen profilin often have oral symptoms in response to eating celery and carrots. In mugwort-celery-spice syndrome, patients sensitised to mugwort cross-react to profilins in celery and spices of the Apiaceae, or Umbelliferae, family (carrots, caraway seeds, parsley, coriander, aniseed or fennel seeds). However, there is a wide range of homology between profilins from different fruits and vegetables; therefore, cross-reactivity is more likely to occur among foods with high degrees of profilin homology than among those with low homology. Pathogenesis-related proteins (PRs) PR proteins are involved in the defence systems of higher plants and are induced upon infection, wounding or environmental stresses (e.g. drought, flooding, freezing temperature, and ozone). They are classified into 14 families based on similarities such as in their amino acid sequence or enzymatic activities. Importantly, these proteins are stable at low pH and resistant to proteolysis. Not all PR families contain allergens: plant-derived allergens have sequence similarities to PR families 2,3,4,5,8,10, and 14. 29 Approximately 25% of characterised allergens are PRs. As PR proteins are influenced by a number of factors, they may vary depending on the environmental conditions in which the plant grows, and on the particular cultivar of the fruit. Even ripeness and storage conditions affect PR content, with more mature plants having more. Geographical and dietary factors also play a role in sensitisation to fruit or vegetables containing PRs. For example, allergy to Rosaceae family fruits is attributed to grass pollen sensitisation in southern Europe and to birch pollen sensitisation in northern Europe. The PR family consists of, among others, the beta 1,3 glucanases (the PR-2 family), the class I, II, and IV chitinases (the PR-3 family), thaumatin-like proteins (PR-5), class III chitinases (PR-8), Bet v 1 homologues (PR-10) and LTPs (PR-14). The PR-2 family consists of beta 1,3 glucanases, which catalyse the hydrolytic cleavage of 1,3 beta-D-glucosidic beta 1,3 glucans, abundant components of the plant cell wall. These allergens have been isolated from banana, potato, tomato and latex (Hev b 2), and are thought to be responsible for the cross-reactivity between these foods and latex in the latex-food syndrome seen in some patients. The PR-3 family consists of the class I, II, and IV chitinases. However, only class I chitinases have been associated with allergy. These proteins hydrolyse chitin found in the exoskeletons of insects and the cell walls of fungi. Banana, avocado and chestnut have allergens with sequence similarity to the class I chitinases, and the class I chitinases have an N-terminal hevein domain that is shared by latex prohevein (Hev b 6.01). The PR-3 allergens are thought to be responsible for the cross-reactivity between the above foods and latex in latex-food syndrome. The PR-5 family contains the thaumatin-like proteins. Although not fully understood, thaumatin-like proteins are thought to have antifungal properties, to rapidly accumulate in high levels during stress on the plant, and to give plants resistance to freezing and drought. Thaumatin-like proteins have been characterised in apple (Mal d 2), cherry (Pru av 2), bell pepper (Cap a 1) and mountain cedar pollen (Jun a 3). The PR-8 family of proteins consists of class III chitinases. These are usually minor allergens. This group includes the latex allergen hevamine and a chitinase from cucumber. The PR-10 family consists of the Bet v 1-homologues, i.e. proteins that have an amino acid sequence homology with the allergen Bet v 1 from birch pollen, a protein with unknown function. As with other PRs, their expression is induced upon environmental stress, wounding or infection. They are probably the most important PR proteins involved in OAS/PFS, with approximately 70% of birch-pollen-allergic individuals being affected by OAS/PFS as a result of IgE crossreactivity between Bet v 1 and its food homologues. PR-10 homologues are found in many members of the Rosaceae and Prunoideae fruits, and of the Apiaceae vegetables. The best known Bet v 1 homologue is Mal d 1, a major allergen in ripe apples, resulting in oral symptoms in birch-pollen-allergic patients. Other Bet v 1-homologues include Pru av 1 from cherry, Pru ar 1 from apricot, Pyr c 1 from pear, Api g 1 from celery, Dau c 1 from carrot, and Cor a 1 from hazelnut. These proteins share a high degree of amino acid sequence similarity (28-67%) with the major birch allergen Bet v 1. The PR-14 family comprises the LTPs. LTPs transfer phospholipids from liposomes to mitochondria and have antimicrobial activities. LTPs are important allergens of the Prunoideae family (peaches, apricots, plums, cherries) and the Rosaceae family (apples, pears), and are usually found in the peel. Significantly different from the protein families involved in OAS/FPS where a pre-existing pollen allergy sensitisation is found, LTPs often cause food allergy to fruit in the absence of pollen allergy. For example, hypersensitivity to peach, the most frequent fruit allergy in Spain, is clinically not associated with any kind of particular pollen allergy, even though there seems to be a higher prevalence of asthma in pollen-allergic patients with peach allergy. There are exceptions. For example, the LTP from mugwort pollen has been shown to crossreact with peach LTP and may be involved in the mugwort-peach allergy association frequently seen in the Mediterranean. Mugwort is not found in South Africa. Individuals who are allergic to LTPs in fruit have been shown to have a higher rate of anaphylaxis (36%) than those sensitised to PR-10 fruit allergens (18%). Current Allergy & Clinical Immunology, June 2009 Vol 22, No. 2 59 Cross-reactive carbohydrate determinants The role of cross-reactive carbohydrate determinants (CCDs) remains controversial. Glycoproteins contain Nlinked carbohydrate groups, which induce IgE, leading to cross-reactivity between foods and pollens. CCDs are found in, among others, celery, tomato, potato and peanut, and in ragweed, timothy grass and birch pollen. However, debate continues over whether these CCDs can cause clinical symptoms. For example, in a study of patients with grass-pollen allergy who are clinically asymptomatic to ingested peanut but have positive serum IgE to peanut but negative reactions to a skin-prick test for peanut, the patients were found to have IgE to the CCDs of peanut. The cross-reactive IgE had low biological activity. In contrast, in a study of celery-allergic patients, 25% were shown to have IgE to CCDs. In a study of the sera of 10 tomato-allergic patients, 4 with IgE to CCDs showed biological activity in the basophil histamine release assay with tomato glycoproteins only but failed to react to nonglycosylated recombinant tomato proteins. IgE antibodies directed toward glycans appear to show the widest pattern of cross-reactivity among allergenic extracts and are often responsible for observed in vitro cross-reactions within PFS. Further research may elucidate the reasons for conflicting evidence and the causes of the variability of biological activity of CCDs. Importantly, many glycoproteins carry only one IgE-binding glycan and therefore cannot cross-link IgE bound to receptors; nor can they induce activation of mast cells and basophils, whereas other glycoproteins have been identified that contain more than one N-linked glycan. As plant proteins are characterised in more detail, it will become easier to identify potential cross-reactions. However, not all patients with cross-reactive antibodies will actually experience symptoms; i.e. the IgE crossreactivity will be either clinically manifest or irrelevant. Clinical manifestations seem to be influenced by a number of factors, including the host’s immune response, allergen exposure, and the individual allergen itself. For example, and importantly, amino acid sequence homology among members of each protein family group varies, which influences the cross-reactivity patterns seen and the likelihood of symptomatic cross-reactivity. For example, in the PR-14 family of LTPs, there is in general a high sequence homology among the allergen members, suggesting a high probability of cross-reactivity among members, and this is confirmed clinically, whereas in the profilin protein family a much wider range of homology exists among members, and therefore cross-reactivity among some plants containing profilin is not certain. Other factors that influence cross-reactivity among family members are the degree of ripeness of the fruit or vegetable, storage conditions, and a number of other factors that influence the expression of the allergen; levels of cross-reactivity may even vary among cultivars. Food-allergic patients may be sensitised to more than one allergen found in a specific food, complicating cross-reactivity. For example, a high prevalence of OAS/FPS occurs to ingestion of apple in birch pollensensitised individuals as a result of the cross-reactivity between Mal d 1 from apple and Bet v 1 from birch pollen; however, apple-allergic individuals may be monosensitised or polysensitised to any number of apple allergens, e.g. to Mal d 1 (PR-10), Mal d 2 (PR-5), Mal d 3 (PR-14), Mal d 4 (profilin), or any other apple allergen or combination of allergens. CLINICAL MANIFESTATIONS The clinical effects are usually restricted to the oral cavity and include oral pruritus, swelling of the lips, tongue and throat, hoarseness, pharyngitis, and laryngeal oedema. The most common complaint among patients is an itching or tingling of the mouth after ingestion of fresh fruit or vegetables. Patients may also experience angio-oedema localised to the mouth. Some studies have shown that a few patients will develop some abdominal cramping or discomfort after ingestion, but rarely vomiting or diarrhoea. Anaphylaxis may uncommonly occur in association with OAS/FSP (as opposed to anaphylaxis without this association). Anaphylaxis is particularly more likely with LTP-containing foods. Almost all patients will have some degree of allergic rhinitis or conjunctivitis because the IgE antibodies to an aeroallergen are cross-reacting with the fruit or vegetable proteins. Reactions may vary depending on the allergen responsible for symptoms. Patients allergic to profilin may report that ingesting a cooked fruit or vegetable does not elicit symptoms, whereas cooked fruit or vegetables containing heat-stable allergens, e.g. LTPs, may still result in symptoms.