P02 (2026 - 2030) Development and function of differently glycosylated IgE antibodies

Marc Ehlers (UzL)

Project Summary

Allergen-specific IgE antibodies can induce allergic reactions by binding to the high-affinity IgE receptor FcεRI on mast cells and basophils. However, healthy individuals can express allergen-specific IgE antibodies without exhibiting allergic symptoms. Furthermore, allergen-specific IgG antibodies, which are also induced by allergen-specific immunotherapy (AIT), can inhibit IgE responses via allergen neutralization and via cross-linking of the IgG inhibitory receptor FcgRII. Interestingly, neither the allergen-specific IgE titer nor the IgG (subclass) titer nor the IgE/IgG ratio can predict the development and severity of allergic disease or the success of AIT.

Our preliminary studies suggest that differentially galactosylated and sialylated allergen-specific IgE antibodies have different potentials to activate mast cells and basophils, although the precise role of IgE glycosylation remains controversial. This project will test the hypothesis that different allergen-specific T and B cell immune responses with distinct inflammatory potentials induce differentially galactosylated and sialylated IgE antibodies and will investigate the impact on allergy development. The results are expected to elucidate the role of IgE glycosylation for FceRI-mediated effector cell activation and release of allergic mediators in murine models and later translate these findings to improve the efficacy of AIT in allergic patients.