IgE-blocking antibodies following SLIT with recombinant Mal d 1 accord with improved apple allergy
Authors: Gabriela Sánchez Acosta, Tamar Kinaciyan, Claudia Kitzmüller, Christian Möbs, Wolfgang Pfützner, Barbara Bohle
Journal: Journal of Allergy and Clinical Immunology (2020)

BackgroundWe 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.ObjectiveWe compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups.MethodsPre- 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 nontreated 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.ResultsSLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1–specific IgG1, IgG2, IgG3, and IgG4 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.ConclusionrMal d 1 SLIT for 16 weeks 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 in birch pollen–related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment. 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. We compared the quantity, quality, and IgE-blocking bioactivity of SLIT-induced Mal d 1-specific IgG antibodies in both treatment groups. 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 nontreated 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. SLIT with rMal d 1 and rBet v 1 induced comparable levels of rMal d 1–specific IgG1, IgG2, IgG3, and IgG4 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. rMal d 1 SLIT for 16 weeks 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 in birch pollen–related food allergy and indicate a dominant protective role of functional IgE-blocking IgG1 antibodies in the early phase of allergy treatment.