Efficacy and safety of 4 months of sublingual immunotherapy with recombinant Mal d 1 and Bet v 1 in patients with birch pollen–related apple allergy

Background Birch pollen–related apple allergy is among the most prevalent food allergies in adolescent/adult subjects and mainly results from sensitization to the major birch pollen allergen Bet v 1 and subsequent cross-reaction with the apple protein Mal d 1. However, specific immunotherapy with birch pollen has inconsistent effects on apple allergy. Objective We sought to compare the safety and efficacy of sublingual immunotherapy (SLIT) with 2 formulations containing either rMal d 1 or rBet v 1 on birch pollen–related apple allergy. Methods Sixty participants with birch pollen–related apple allergy were randomized to daily sublingual application of placebo (n = 20) or 25 μg of rMal d 1 (n = 20) or rBet v 1 (n = 20) for 16 weeks. Adverse events were regularly recorded. Sublingual challenges with standardized doses of rMal d 1, skin prick tests with recombinant allergens, and measurements of allergen-specific IgE and IgG 4 antibodies were performed before and after treatment. Results Both formulations caused comparable, mainly local adverse events. No systemic reactions occurred. Compared with the placebo and rBet v 1–treated groups, SLIT with rMal d 1 reduced rMal d 1–induced oral symptoms ( P  = .001 and P  = .038) accompanied by longitudinally reduced rMal d 1–specific cutaneous reactions ( P  = .022) and enhanced IgG 4 /IgE ratios ( P  = .012). SLIT with rBet v 1 neither improved the clinical reactivity to rMal d 1 nor enhanced rMal d 1–specific IgG 4 /IgE ratios. Participants receiving placebo showed no allergen-specific changes. Conclusion Sublingual treatment with a recombinant food allergen was safe and clinically effective, as determined by using standardized challenges. We present a promising approach for the effective treatment of birch pollen–related apple allergy.