Available online 7 July 2025

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What is already known about this topic?

Approximately 70% of patients with birch pollen allergy develop a pollen food allergy syndrome, particularly to apples. To date, there is no standardized therapy available for treating this cross-reactive allergy.•

What does this article add to our knowledge?

Consumption of increasing doses of fresh apples induces a stable and robust tolerance in birch pollen-allergic patients with pollen food allergy syndrome.•

How does this study impact current management guidelines?

This study introduces a potential treatment option, promoting tolerance development through regular apple consumption, by offering a globally applicable therapeutic protocol for clinical practice.

ABSTRACTBackground

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. Afterwards, 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 skin prick test with 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 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.

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© 2025 Published by Elsevier Inc. on behalf of the American Academy of Allergy, Asthma & Immunology