IgE, IgG4 and IgA specific to Bet v 1-related food allergens do not predict oral allergy syndrome

About 70% of patients allergic to birch pollen (BP) show IgE-mediated reactions to plant foods such as hazelnut, apple, stone fruits, kiwi, carrot, celeriac and soya bean, typically mild reactions of the upper oral cavity, termed oral allergy syndrome (OAS) 1. These food allergies are a consequence of sensitization to Bet v 1 and subsequent IgE and T-cell cross-reactivity with homologous food allergens 2,3, such as Cor a 1.04 4, Mal d 1 5, Pru p 1 6, Api g 1 7,8 and Gly m 4 9. These allergens possess high sequence and structural identities with Bet v 1 10,11. Nearly all BP-allergic patients are sensitized to Bet v 1 12,13 and are at risk of developing plant food allergy 14. However, most patients show allergic reactions only to a limited number of potentially allergenic foods. Moreover, IgE specific to a certain Bet v 1-related allergen does not predict a clinically manifest allergy 15. The factors that determine the clinical spectrum of Bet v 1-associated plant food allergy are mostly unknown. In contrast to IgE, Bet v 1-specific antibodies of other isotypes were less frequently investigated. Some patients undergoing allergen-specific immunotherapy (IT) develop blocking IgG which inhibits binding of allergens to IgE 16. Moreover, IgG4, IgG4/IgE ratios and IgG4 blocking activity were associated with tolerance to hazelnut and apple among Bet v 1-sensitized patients 13. Few studies examining the role of allergen-specific IgA have been published. The levels of Bet v 1-specific IgA in nasal fluids of BP-allergic children increased during the pollen season, albeit with unclear clinical relevance 17. Examinations of the significance of IgA for the development of natural or induced tolerance in milk- or egg-allergic children showed no correlation 18,19. Hence, we aimed to determine whether potentially tolerance-inducing allergen-specific IgG and IgA antibodies have an influence on the clinical activity of allergen-specific IgE. To this end, we used a panel of sera from well-characterized BP-allergic patients with individual patterns of plant food allergies to measure IgE, IgG1, IgG4 and IgA levels specific to Bet v 1-related allergens from hazelnut, peach, apple, soya, mung bean and celeriac. Moreover, we compared these concentrations with clinical symptoms to evaluate the significance of the different Ig classes in context with allergy or tolerance.