Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model

Abstract

IgE causes anaphylaxis in type I hypersensitivity diseases by activating degranulation of effector cells such as mast cells and basophils. The mechanisms that control IgE activity and prevent anaphylaxis under normal conditions are still enigmatic. We aimed to unravel how anti-IgE autoantibodies are induced and we aimed to understand their role in regulating serum IgE level and allergic anaphylaxis. We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analyzed the effect of those antibodies on serum kinetics and their invitro and invivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera. Immunization of mice with IgE-immune complexes induced glycan-specific anti-IgE autoantibodies. The anti-IgE autoantibodies prevented effector cell sensitization, reduced total IgE serum levels, protected mice from passive and active IgE sensitization, and resulted in cross-protection against different allergens. Furthermore, glycan-specific anti-IgE autoantibodies were present in sera from subjects with allergy and subjects without allergy. In conclusion, this study provided the first evidence that in the murine model, the serum level and anaphylactic activity of IgE may be downregulated by glycan-specific IgG anti-IgE autoantibodies.