Fruit allergy: from sensitization and symptoms to prevention and treatment

Abstract

It is generally assumed that the incidence of allergies in the Western world has been rising over the past few decades. Apple allergy was chosen as a model system because apples are widely consumed in Europe and they frequently cause allergic reactions with a variable degree of severity. In Northern and Central Europe, apple allergy has always been described as a mild disease. More recent observations from Southern European countries indicate that apple can induce severe systemic reactions as well. Chapter 2 describes the apple allergic patients from Austria, Italy, Spain and The Netherlands. Different sensitization patterns were studied RAST, SPT and. clinical histories were studied. Our studies in four European countries have confirmed that the presence of birch trees is a dominant factor in sensitization to the major apple allergen Mal d 1. Primary sensitization to the major birch pollen allergen Bet v 1 is at the basis of IgE recognition of Mal d 1 in Northern and Central Europe. Apple allergy (LTP) in Spain is most likely a result of primary sensitization to peach. It can also not be ruled out completely that specific pollen in the Mediterranean are at the basis of LTP sensitization. In Chapters 3 and 4 two novel forms of cross-reactive food allergies among birch pollen allergic patients are presented, i.e. to jackfruit and sharonfruit. In both cases patients reacted on the first exposure to the fruit involved and more severely than they used to do on apple and other fruits. These studies suggest that some food homologs of Bet v 1 might be more stable than the extremely labile Mal d 1 from apple. Jackfruit and sharonfruit allergy can be added to the list of birch pollen related food allergies. Increased consumption of these fruits will result in a rise in allergic symptoms. Treatment of food allergic patients is primarily based on avoidance diets. Such diets can have a considerable social impact and lead to nutritional deficiencies. In Chapter 5 the allergenicity of different apple cultivars was assessed by SPT and double-blind, placebo controlled food challenge to develop hypoallergenic fruit. Chapter 6 describes the development of a hypoallergenic apple plant in which the Mal d 1 gene was knocked out by RNA interference. Using leaf material of young plantlets for SPT and immunoblot, it was demonstrated that Mal d 1 activity was indeed reduced significantly in the mutant plantlets. Public opinion on genetically modified foods has proven to be perhaps a bigger hurdle. The attitude of the allergic patients towards hypoallergenic genetically modified foods was investigated and described in Chapter 7. Finally, two chapters focus on strategies for allergen-specific immunotherapy. Specific immunotherapy is not used to treat food allergies. A major problem of immunotherapy using food allergens is the risk of severe side effects, including anaphylactic shock. In Chapter 8, a study using birch pollen immunotherapy trial is described in which the effect on cross-reactive apple allergy is evaluated by SPT and DBPCFC. Our clinical trial supports earlier claims that birch pollen immunotherapy has a beneficial effect on cross-reactive food allergies. In Chapter 9, a recently developed hypoallergenic mutant of the major apple allergen Mal d 1 is evaluated in vivo using SPT and DBPCFC. It was demonstrated that the mutant indeed behaved as a hypoallergen. Hypoallergenic mutants are potential candidates for future use in immunotherapy.