Glycobiology of IgE

Abstract

Antibodies play a vital role in the immune system, with distinct isotypes having unique tropisms and performing specialized functions. Of these isotypes, IgE is the least abundant in circulation yet plays a critical role in defense against parasitic infection and allergic reactions. IgE is also heavily N-linked glycosylated, a posttranslational modification that influences receptor interactions of effector responses. The importance of glycosylation on IgG function is well established, and the roles of IgE glycans are emerging. This review examines the relationship between IgE glycosylation and its biological function. IgE glycosylation, specifically the oligomannosidic glycan, is necessary for IgE binding to its high-affinity receptor FcεRI on mast cells and basophils. Recent evidence suggests that terminal sialic acid residues on complex biantennary glycans significantly enhance IgE's allergic potential, with sialylation of IgE demonstrating reduced capacity to trigger degranulation and anaphylaxis. Glycosylation also influences IgE's interaction with its low-affinity receptor FcεRII/CD23, affecting serum clearance and antigen presentation. Beyond allergy, this review also covers IgE's impacts on its roles in autoimmunity, parasite defense, and protection against venoms. Current therapeutic approaches targeting IgE include monoclonal antibodies like omalizumab, with emerging therapeutics looking to target systemic IgE production mechanisms also covered. Although the understanding of IgG glycosylation is known, there is much to uncover in terms of IgE glycosylation, which may open new avenues for developing more precise interventions that modulate its effector functions.