Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model

Paul Engeroff; Kevin Plattner; Federico Storni; Franziska Thoms; Kayluz Frias Boligan; Lukas Muerner; Alexander Eggel; Stephan von Gunten; Martin F Bachmann; Monique Vogel

doi:10.1016/j.jaci.2020.11.031

Glycan-specific IgG anti-IgE autoantibodies are protective against allergic anaphylaxis in a murine model

J Allergy Clin Immunol. 2021 Apr;147(4):1430-1441. doi: 10.1016/j.jaci.2020.11.031. Epub 2020 Dec 9.

Affiliations

¹ University Hospital for Rheumatology, Immunology, and Allergology, University of Bern, Bern, Switzerland; Department of BioMedical Research, University of Bern, Bern, Switzerland; Graduate School of Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland.
² Department of Dermatology, Zurich University Hospital, Zurich, Switzerland.
³ Institute of Pharmacology, University of Bern, Bern, Switzerland.
⁴ University Hospital for Rheumatology, Immunology, and Allergology, University of Bern, Bern, Switzerland; Department of BioMedical Research, University of Bern, Bern, Switzerland.
⁵ University Hospital for Rheumatology, Immunology, and Allergology, University of Bern, Bern, Switzerland; Department of BioMedical Research, University of Bern, Bern, Switzerland; Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom.
⁶ University Hospital for Rheumatology, Immunology, and Allergology, University of Bern, Bern, Switzerland; Department of BioMedical Research, University of Bern, Bern, Switzerland. Electronic address: monique.vogel@dbmr.unibe.ch.

PMID: 33309740
DOI: 10.1016/j.jaci.2020.11.031

Abstract

Background: IgE causes anaphylaxis in type I hypersensitivity diseases by activating degranulation of effector cells such as mast cells and basophils. The mechanisms that control IgE activity and prevent anaphylaxis under normal conditions are still enigmatic.

Objective: We aimed to unravel how anti-IgE autoantibodies are induced and we aimed to understand their role in regulating serum IgE level and allergic anaphylaxis.

Methods: We immunized mice with different forms of IgE and tested anti-IgE autoantibody responses and their specificities. We then analyzed the effect of those antibodies on serum kinetics and their in vitro and in vivo impact on anaphylaxis. Finally, we investigated anti-IgE autoantibodies in human sera.

Results: Immunization of mice with IgE-immune complexes induced glycan-specific anti-IgE autoantibodies. The anti-IgE autoantibodies prevented effector cell sensitization, reduced total IgE serum levels, protected mice from passive and active IgE sensitization, and resulted in cross-protection against different allergens. Furthermore, glycan-specific anti-IgE autoantibodies were present in sera from subjects with allergy and subjects without allergy.

Conclusion: In conclusion, this study provided the first evidence that in the murine model, the serum level and anaphylactic activity of IgE may be downregulated by glycan-specific IgG anti-IgE autoantibodies.

Keywords: Anti-IgE autoantibodies; IgE regulation; allergy; glycans; hypersensitivity.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Allergens / administration & dosage
Animals
Antibodies, Anti-Idiotypic / immunology*
Autoantibodies / immunology*
Disease Models, Animal
Glycoproteins / administration & dosage
Humans
Hypersensitivity / immunology*
Immunoglobulin E / administration & dosage
Immunoglobulin G / immunology*
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Knockout
Polysaccharides / immunology*

Substances

Allergens
Antibodies, Anti-Idiotypic
Autoantibodies
Glycoproteins
Immunoglobulin G
Polysaccharides
anti-IgE antibodies
Immunoglobulin E
Fel d 1 protein, Felis domesticus

Grants and funding

R01 HL141493/HL/NHLBI NIH HHS/United States