IgE Sialylation is a Determinant of Allergic Pathogenicity

Approximately one-third of the world’s population suffers from allergies(1). Allergen exposure crosslinks mast cell- and basophil-bound immunoglobulin E (IgE), triggering the release of inflammatory mediators, including histamine(2). Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations do not reproducibly correlate with allergic disease(3–5). It is well-established that glycosylation of IgG dictates its effector function and has disease-specific patterns. However, whether IgE glycans differ in disease states or impact biological activity is completely unknown(6). We therefore unbiasedly examined glycosylation patterns of total IgE from peanut-allergic and non-atopic individuals. This revealed an increase in sialic acid content on total IgE from peanut-allergic individuals compared to non-atopic subjects. Sialic acid removal from IgE attenuated effector cell degranulation and anaphylaxis in multiple functional models of allergic disease. Therapeutic interventions, including sialic acid removal from cell-bound IgE with a FcεRI targeted-neuraminidase, or administration of asialylated IgE, markedly reduced anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.