Efficacy of Birch-pollen Immunotherapy on Cross-reactive Food Allergy Confirmed by Skin Tests and Double-blind Food Challenges

Background: The effect of birch-pollen immunotherapy (IT) on cross-reactive food allergies is controversial.

Objective: The aim of this study was to investigate the effect of birch-pollen IT on apple allergy and to evaluate recombinant allergens and double-blind placebo-controlled food challenges (DBPCFCs) as monitoring tools.

Methods: Twenty-five adult birch-pollen- and apple-allergic patients were randomly divided into two groups, either receiving birch-pollen IT or symptomatic drugs only. IgE and IgG4 antibodies against birch pollen, apple, natural Bet v 1 and Mal d 1 were measured. In addition, skin prick tests (SPT) were performed using recombinant Bet v 1 (rBet v 1) and Mal d 1 (rMal d 1). Clinical outcome was evaluated by DBPCFC. CD4(+)CD25(+) regulatory T cells (Tregs) were isolated from peripheral blood and tested in functional assays.

Results: Birch-pollen IT resulted in a significant decrease of SPT reactivity for rBet v 1 (30-fold) and rMal d 1 (10-fold) already after 3 months. IgG4 antibodies were potently induced against Bet v 1, displaying cross-reactivity to Mal d 1. Visual analogue scale scores decreased >10-fold in 9/13 patients of the IT group, with three patients converting to negative. In the control group, no decrease was observed. Birch-pollen IT did not lead to detectable changes in the number or function of the CD4(+)CD25(+) Tregs.

Conclusions: This trial supports the claims that birch-pollen IT also decreases allergy to foods containing Bet v 1-homologous allergens. Recombinant allergens and DBPCFCs have proven to be useful tools for monitoring the effect of birch-pollen IT on linked food allergies.