Shade, Kai-TingConroy, MichelleWashburn, NathanielKitaoka, MayaHuynh, DanielLaprise, EmmaPatil, Sarita U.Shreffler, WayneAnthony, Robert M.Anthony, R2022-08-312020-05-20Shade, Kai-Ting C, Conroy, Michelle E, Washburn, Nathaniel, Kitaoka, Maya, Huynh, Daniel J, Laprise, Emma, Patil, Sarita, Shreffler, Wayne, and Anthony, Robert M. "IgE Sialylation Is a Determinant of Allergic Pathogenicity." Nature (London) 582, no. 7811 (2020): 265-70.0028-08361476-4687https://nrs.harvard.edu/URN-3:HUL.INSTREPOS:37373117Approximately one-third of the world’s population suffers from allergies1. Allergen exposure crosslinks mast cell- and basophil-bound immunoglobulin E (IgE), triggering the release of inflammatory mediators, including histamine2. Although IgE is absolutely required for allergies, it is not understood why total and allergen-specific IgE concentrations do not reproducibly correlate with allergic disease3-5. 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 unknown6. 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.en-USMultidisciplinaryJournal Article2022-08-3110.1038/s41586-020-2311-z