Engeroff, Paul; Plattner, Kevin; Storni, Federico; Storni, Federico; Thoms, Franziska; Frias Boligan, Kayluz; Mürner, Lukas; Eggel, Alexander; von Gunten, Stephan; Bachmann, Martin F.; Vogel, Monique (2021). Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model. Journal of allergy and clinical immunology, 147(4), pp. 1430-1441. Elsevier 10.1016/j.jaci.2020.11.031
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BACKGROUND
IgE causes anaphylaxis in type-1 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.
OBJECTIVE
We aimed to unravel how anti-IgE autoantibodies are induced and understand their role in regulating serum IgE level and allergic anaphylaxis.
METHODS
We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analysed the effect of those antibodies on serum kinetics and their in vitro and in vivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera.
RESULTS
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 allergic and non-allergic subjects.
CONCLUSION
In conclusion, we provide first evidence that in the murine model the serum level and anaphylactic activity of IgE may be down-regulated by glycan-specific IgG anti-IgE autoantibodies.