Sialylation of immunoglobulin E is a determinant of allergic pathogenicity

• Published in: Nature (London) Vol. 582; no. 7811; pp. 265 - 270
• Main Authors: Shade, Kai-Ting C, Conroy, Michelle E, Washburn, Nathaniel, Kitaoka, Maya, Huynh, Daniel J, Laprise, Emma, Patil, Sarita U, Shreffler, Wayne G, Anthony, Robert M
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.06.2020
• Subjects: Acids; Adolescent; Adult; Aged; Allergens; Allergens - immunology; Allergic diseases; Allergies; Anaphylaxis; Anaphylaxis - immunology; Animals; Antibodies; Atopy; Biological activity; Case-Control Studies; Cell Degranulation - immunology; Child; Child, Preschool; Crosslinking; Degranulation; Disease; Enzymes; Exo-a-sialidase; Fc receptors; Female; Food allergies; Glycosylation; Health aspects; Histamine; Humans; Immunoglobulin E; Immunoglobulin E - adverse effects; Immunoglobulin E - chemistry; Immunoglobulin E - immunology; Immunoglobulin E - pharmacology; Immunoglobulin G; Immunoglobulins; Infant; Infant, Newborn; Inflammation; Influenza; Leukocytes (basophilic); Male; Mast cells; Mice; Middle Aged; Models, Immunological; N-Acetylneuraminic Acid - analysis; N-Acetylneuraminic Acid - chemistry; N-Acetylneuraminic Acid - metabolism; Neuraminidase - metabolism; Pathogenicity; Pathogens; Peanut Hypersensitivity - immunology; Peanut Hypersensitivity - pathology; Peanuts; Polysaccharides; Receptors, IgE - metabolism; Therapeutic applications; Young Adult; United States
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/s41586-020-2311-z

Approximately one-third of the world's population suffers from allergies . Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, triggering the release of inflammatory mediators, including histamine . 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 . 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 unknown . 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.