PMID- 32499653 OWN - NLM STAT- MEDLINE DCOM- 20200709 LR - 20220122 IS - 1476-4687 (Electronic) IS - 0028-0836 (Print) IS - 0028-0836 (Linking) VI - 582 IP - 7811 DP - 2020 Jun TI - Sialylation of immunoglobulin E is a determinant of allergic pathogenicity. PG - 265-270 LID - 10.1038/s41586-020-2311-z [doi] AB - Approximately one-third of the world's population suffers from allergies(1). Exposure to allergens crosslinks immunoglobulin E (IgE) antibodies that are bound to mast cells and basophils, 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 affect biological activity is completely unknown(6). 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 FcepsilonRI, and administering asialylated IgE-markedly reduce anaphylaxis. Together, these results establish IgE glycosylation, and specifically sialylation, as an important regulator of allergic disease. FAU - Shade, Kai-Ting C AU - Shade KC AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Conroy, Michelle E AU - Conroy ME AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Washburn, Nathaniel AU - Washburn N AUID- ORCID: 0000-0003-1127-1909 AD - Momenta Pharmaceuticals Inc, Cambridge, MA, USA. FAU - Kitaoka, Maya AU - Kitaoka M AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Huynh, Daniel J AU - Huynh DJ AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Laprise, Emma AU - Laprise E AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. FAU - Patil, Sarita U AU - Patil SU AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Division of Pediatric Allergy and the MGH Food Allergy Center, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Food Allergy Science Initiative at the Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. FAU - Shreffler, Wayne G AU - Shreffler WG AUID- ORCID: 0000-0001-6465-137X AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Division of Pediatric Allergy and the MGH Food Allergy Center, Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. AD - Food Allergy Science Initiative at the Broad Institute of the Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA. FAU - Anthony, Robert M AU - Anthony RM AD - Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. robert.anthony@mgh.harvard.edu. LA - eng GR - R01 AI139669/AI/NIAID NIH HHS/United States GR - U19 AI095261/AI/NIAID NIH HHS/United States GR - K12 HL141953/HL/NHLBI NIH HHS/United States GR - K23 AI121491/AI/NIAID NIH HHS/United States GR - P30 DK043351/DK/NIDDK NIH HHS/United States GR - T32 AR007258/AR/NIAMS NIH HHS/United States GR - 5U19 AI095261-03/NH/NIH HHS/United States GR - DP2 AR068272/AR/NIAMS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20200520 PL - England TA - Nature JT - Nature JID - 0410462 RN - 0 (Allergens) RN - 0 (Receptors, IgE) RN - 37341-29-0 (Immunoglobulin E) RN - EC 3.2.1.18 (Neuraminidase) RN - GZP2782OP0 (N-Acetylneuraminic Acid) SB - IM CIN - Nat Rev Immunol. 2020 Jul;20(7):408-409. PMID: 32514034 CIN - Immunol Cell Biol. 2020 Sep;98(8):617-619. PMID: 32632971 MH - Adolescent MH - Adult MH - Aged MH - Allergens/immunology MH - Anaphylaxis/immunology MH - Animals MH - Case-Control Studies MH - Cell Degranulation/immunology MH - Child MH - Child, Preschool MH - Female MH - Glycosylation MH - Humans MH - Immunoglobulin E/adverse effects/*chemistry/*immunology/pharmacology MH - Infant MH - Infant, Newborn MH - Male MH - Mice MH - Middle Aged MH - Models, Immunological MH - N-Acetylneuraminic Acid/*analysis/chemistry/metabolism MH - Neuraminidase/metabolism MH - Peanut Hypersensitivity/*immunology/*pathology MH - Receptors, IgE/metabolism MH - Young Adult PMC - PMC7386252 MID - NIHMS1575439 COIS- Competing interests The authors declare no competing interests. EDAT- 2020/06/06 06:00 MHDA- 2020/07/10 06:00 PMCR- 2020/11/20 CRDT- 2020/06/06 06:00 PHST- 2019/05/13 00:00 [received] PHST- 2020/03/11 00:00 [accepted] PHST- 2020/06/06 06:00 [pubmed] PHST- 2020/07/10 06:00 [medline] PHST- 2020/06/06 06:00 [entrez] PHST- 2020/11/20 00:00 [pmc-release] AID - 10.1038/s41586-020-2311-z [pii] AID - 10.1038/s41586-020-2311-z [doi] PST - ppublish SO - Nature. 2020 Jun;582(7811):265-270. doi: 10.1038/s41586-020-2311-z. Epub 2020 May 20.