biostudies-literatureShade KCNIDDK NIH HHSNIAID NIH HHSNHLBI NIH HHSNIAMS NIH HHSNIH HHS265-270https://www.ebi.ac.uk/biostudies/studies/S-EPMC7386252biostudies-literatureUnknown582(7811)Approximately one-third of the world's population suffers from allergies¹. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, 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 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 affect biological activity is completely unknown⁶. Here we perform an unbiased examination of glycosylation patterns of total IgE from individuals with a peanut allergy and from non-atopic individuals without allergies. Our analysis reveals an increase in sialic acid content on total IgE from individuals with a peanut allergy compared with non-atopic individuals. Removal of sialic acid from IgE attenuates effector-cell degranulation and anaphylaxis in several functional models of allergic disease. Therapeutic interventions-including removing sialic acid from cell-bound IgE with a neuraminidase enzyme targeted towards the IgE receptor FcεRI, and administering asialylated IgE-markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.NatureSialylation of immunoglobulin E is a determinant of allergic pathogenicity.PMC7386252DP2 AR068272K23 AI121491K12 HL1419535U19 AI095261-03R01 AI139669P30 DK043351T32 AR007258U19 AI095261Shade KCHuynh DJKitaoka MShreffler WGPatil SUConroy MELaprise EWashburn NAnthony RMfalseSialylation of immunoglobulin E is a determinant of allergic pathogenicity.Approximately one-third of the world's population suffers from allergies¹. Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, 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 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 affect biological activity is completely unknown⁶. Here we perform an unbiased examination of glycosylation patterns of total IgE from individuals with a peanut allergy and from non-atopic individuals without allergies. Our analysis reveals an increase in sialic acid content on total IgE from individuals with a peanut allergy compared with non-atopic individuals. Removal of sialic acid from IgE attenuates effector-cell degranulation and anaphylaxis in several functional models of allergic disease. Therapeutic interventions-including removing sialic acid from cell-bound IgE with a neuraminidase enzyme targeted towards the IgE receptor FcεRI, and administering asialylated IgE-markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease.2020-01-01T00:00:00Z2020 Jun2024-11-09T11:46:48.964Z2021-02-19T18:07:51ZS-EPMC73862523249965310.1038/s41586-020-2311-z