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Oral immunotherapy induces IgG antibodies that act through FcRIIb to suppress IgE-mediated hypersensitivity

Burton, OT;Logsdon, SL;Zhou, JS;Medina-Tamayo, J;Abdel-Gadir, A;Noval Rivas, M;Koleoglou, KJ;Chatila, TA;Schneider, LC;Rachid, R;Umetsu, DT;Oettgen, HC;

Food-induced anaphylaxis is triggered by specific IgE antibodies. Paradoxically, some subjects with significant IgE levels can ingest allergenic foods without incident. Similarly, subjects completing oral immunotherapy (OIT) tolerate food challenges despite persistent high-titer food-specific IgE.,We sought to test whether IgG antibodies induced by food immunotherapy prevent food-induced anaphylaxis and whether this occurs through the inhibitory receptor FcRIIb.,Food allergy-susceptible Il4raF709 mice were enterally sensitized to ovalbumin (OVA). Similarly sensitized IgE-deficient (IgE(-/-)) Il4raF709 mice, which can ingest OVA without anaphylaxis, were subjected to a high-dose enteral OVA desensitization protocol (OIT). Sera from both groups were tested for the ability to activate or inhibit bone marrow mast cells (BMMCs) exposed to allergen or to passively transfer allergy to naive hosts. In parallel experiments sera obtained from patients with peanut allergy before and after undergoing OIT were interrogated for their ability to enhance or suppress peanut-induced activation in an indirect assay by using basophils from nonallergic donors.,Il4raF709 mice exhibited strong OVA-specific IgE responses. Their sera efficiently sensitized BMMCs for activation by antigen challenge. Sera from Il4raF709/IgE(-/-) mice subjected to OVA OIT suppressed BMMC responses. This inhibition was IgG mediated and FcRIIb dependent. Similarly, pre-OIT but not post-OIT sera from patients efficiently sensitized basophils for peanut-induced activation. IgG antibodies in post-OIT sera suppressed basophil activation by pre-OIT sera. This inhibition was blocked by antibodies against FcRII.,Food-specific IgG antibodies, such as those induced during OIT, inhibit IgE-mediated reactions. Strategies that favor IgG responses might prove useful in the management of food allergy.