IgE-blocking antibodies following SLIT with recombinant Mal d 1 accord with improved apple allergy.

Abstract Background We recently reported that 16 weeks of sublingual immunotherapy (SLIT) with recombinant (r) Mal d 1, but not rBet v 1, significantly improved birch pollen-related apple allergy. Allergen-specific IgE-blocking IgG antibodies have been associated with clinical efficacy. Objective We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups. Methods Pre- and post-SLIT sera were assessed for rMal d 1-specific IgG antibodies in ELISA and for their ability to inhibit apple allergen-induced upregulation of CD63 on basophils from non-treated individuals with birch pollen-related apple allergy. Post-SLIT sera depleted of IgG1 or IgG4 were compared for their IgE-blocking activity. IgG1-binding to rMal d 1 was competed with rMal d 1 and rBet v 1 in ELISA. Results SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1-specific IgG1-4 antibodies. Only post-rMal d 1-SLIT sera displayed IgE-blocking activity which was significantly reduced by depletion of IgG1 and less so by IgG4-depletion. In competition ELISA, IgG1-binding to Mal d 1 in post-rMal d 1-SLIT sera was fully inhibited with rMal d 1 but not with rBet v 1. Correspondingly, Bet v 1 was the more potent competitor for IgG1-binding to Mal d 1 in post-rBet v 1-SLIT sera. Conclusion Sixteen-week rMal d 1-SLIT induced functional, primarily Mal d 1-specific IgE-blocking antibodies whereas rBet v 1-SLIT induced Bet v 1-specific, Mal d 1-cross-reactive IgG antibodies with limited cross-blocking activity. These results provide a possible explanation for the limited effectiveness of birch pollen immunotherapy on birch pollen-related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment.