Gabriela Sánchez Acosta1, Tamar Kinaciyan2, Claudia Kitzmüller1, Christian Möbs3, Wolfgang Pfützner3, Barbara Bohle4. 1. Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. 2. Department of Dermatology, Medical University of Vienna, Vienna, Austria. 3. Department of Dermatology and Allergology, Philipps-Universität Marburg, Marburg, Germany. 4. Department of Pathophysiology and Allergy Research, Medical University of Vienna, Vienna, Austria. Electronic address: barbara.bohle@meduniwien.ac.at.
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 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. RESULTS: 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. CONCLUSION: 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.
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 appleallergy. 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 nontreated individuals with birch pollen-related appleallergy. 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, 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. CONCLUSION: 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.
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