Efficacy of birch‐pollen immunotherapy on cross‐reactive food allergy confirmed by skin tests and double‐blind food challenges

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Abstract
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.