Structured Fresh Apple Consumption for Birch Pollen Food Allergy Syndrome in an Uncontrolled Phase II/III Trial

Abstract

Background: Birch pollen food allergy syndrome to apples is prevalent, but no approved or standardized treatment exists so far. Objective: To investigate the effect of oral therapy with fresh apples on birch pollen food allergy syndrome to apples using a feasible treatment protocol with different widely available apple cultivars. Methods: In this uncontrolled phase II/III study, 42 apple cultivars were tested for their allergen content in vivo by skin prick tests and oral provocations. Afterward, 36 patients consumed apples of increasing dose and allergenicity over a period of 12 months. Side effects were documented weekly in a clinical diary. Efficacy was tested before and after therapy by oral provocation and a skin prick test with the Golden Delicious apple. Total IgE, specific IgE, and IgG4 for Mal d 1 and inhibition of basophil activation were analyzed before and after treatment. Other cross-reactive foods were determined by a questionnaire before and after therapy. Results: Oral immunotherapy with apples resulted in a consistent and durable tolerance of apples and a significant augmented tolerance to other Bet v 1 cross-reactive foods. After therapy, specific IgG4 antibodies to Mal d 1 increased significantly; simultaneously specific IgE to Mal d 1 and skin prick test reactivity to apples decreased significantly. Moreover, sera of treated patients displayed blocking activity to Mal d 1. Conclusion: Oral allergy-specific immunotherapy with fresh apples is a promising treatment for birch pollen food allergy syndrome to apples and other Bet v 1 cross-reactive foods.