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

• Published in: Journal of allergy and clinical immunology Vol. 147; no. 4; pp. 1430 - 1441
• Main Authors: Engeroff, Paul, Plattner, Kevin, Storni, Federico, Thoms, Franziska, Frias Boligan, Kayluz, Muerner, Lukas, Eggel, Alexander, von Gunten, Stephan, Bachmann, Martin F., Vogel, Monique
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2021; Elsevier Limited
• Subjects: Allergens; Allergens - administration & dosage; allergy; Anaphylaxis; Animal models; Animals; Anti-IgE autoantibodies; Antibodies; Antibodies, Anti-Idiotypic - immunology; Antigen-antibody complexes; Antigens; Asthma; Autoantibodies; Autoantibodies - immunology; Chromatography; Cloning; Cross-protection; Degranulation; Disease Models, Animal; Effector cells; Flow cytometry; Food allergies; glycans; Glycoproteins - administration & dosage; Humans; Hypersensitivity; Hypersensitivity - immunology; IgE regulation; Immunization; Immunoglobulin E; Immunoglobulin E - administration & dosage; Immunoglobulin G; Immunoglobulin G - immunology; Leukocytes (basophilic); Mast cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Polysaccharides - immunology; Proteins; Serum levels; Urticaria; England; United Kingdom > UK; Switzerland; Germany; Endo F1; IgE–Fel d 1; hypersensitivity; PNG F; HRP; allergy; IgE(PNG); IgE regulation; Endo F2; glycans; Anti-IgE autoantibodies; Fel d; IgE(PNG)–Fel d 1; BMMC
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2020.11.031

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. 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. 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. 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. 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.