Successful sublingual immunotherapy with birch pollen has limited effects on concomitant food allergy to apple and the immune response to the Bet v 1 homolog Mal d 1

Background: Cross-reactivity between the major birch pollen allergen, Bet v 1. and the apple protein, Mal d 1, frequently causes food allergy. Objective: To investigate the effects of successful sublingual immunotherapy (SLIT) with birch pollen extract on apple allergy and the immune response to Bet v I and Mal d 1. Methods: Before and after 1 year of SLIT, Bet v 1-sensitized patients with oral allergy syndrome to apple underwent nasal challenges with birch pollen and double-blind placebo-controlled food challenges with apple. Bet v 1-specific and Mal d I-specific serum antibody levels and proliferation in PBMCs and allergen-specific T-cell lines (TCLs) were determined. Bet v I-specific TCLs were mapped for T-cell epitopes. Results: In 9 patients with improved nasal provocation scores to birch pollen, apple-induced oral allergy syndrome was not significantly, reduced. Bet v I-specific IgE and IgG(4) levels significantly increased. Bet v I-specific T-cell responses to all epitopes and those cross-reactive with Mal d I significantly decreased. However, neither Mal d I-specific IgE and IgG4 levels nor Mal d I-induced T-cell proliferation changed significantly. In contrast, Mal d I-specific TCLs showed increased responses to Mal d 1 after I year of SLIT. Conclusion: This longitudinal study indicates that pollen SLIT does not efficiently alter the immune response to pollen-related food allergens. which may explain why pollen-associated food allergy is frequently not ameliorated by pollen immunotherapy even if respiratory symptoms significantly improve. Clinical implications: SLIT with birch pollen may have no clinical effect on associated apple allergy.