Suppression of IgE-mediated anaphylaxis and food allergy with monovalent anti-FcεRIα mAbs.

Anaphylaxis / drug therapy Animals Anti-Allergic Agents / pharmacology Antibodies, Monoclonal / pharmacology Female Food Hypersensitivity / drug therapy Immunoglobulin E / immunology Immunoglobulin G / immunology Male Mast Cells / drug effects Mice, Inbred BALB C Mice, Transgenic Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases / immunology Receptors, IgE / genetics Syk Kinase / immunology
IL-4 IgG(1) IgG(4) Mouse Syk cross-linking desensitization humanized mast cell

Journal

The Journal of allergy and clinical immunology
ISSN: 1097-6825
Titre abrégé: J Allergy Clin Immunol
Pays: United States
ID NLM: 1275002

Informations de publication

Date de publication:
05 2021
Historique:
received: 29 08 2020
revised: 20 10 2020
accepted: 30 10 2020
pubmed: 17 12 2020
medline: 25 9 2021
entrez: 16 12 2020
Statut: ppublish

Résumé

Mast cell and basophil activation by antigen cross-linking of FcεRI-bound IgE is central to allergy pathogenesis. We previously demonstrated global suppression of this process by rapid desensitization with anti-FcεRIα mAbs. We sought to determine whether use of monovalent (mv) anti-FcεRIα mAbs increases desensitization safety without loss of efficacy. mv anti-human (hu) FcεRIα mAbs were produced with mouse-derived immunoglobulin variable regions and huIgG mv anti-hu FcεRIα mAbs are considerably less able than divalent mAbs are to induce anaphylaxis and deplete mast cell and basophil IgE, but mv mAbs still strongly suppress IgE-mediated disease. The mv mAbs can be safely administered as a single large dose to mice with typical susceptibility to anaphylaxis, while a rapid desensitization approach safely suppresses disease in mice with increased susceptibility. Our huIgG mv anti-FcεRIα mAbs more safely suppress IgE-mediated anaphylaxis and food allergy than divalent variants of the same mAbs do. These mv mAbs may be useful for suppression of huIgE-mediated disease.

Sections du résumé

BACKGROUND
Mast cell and basophil activation by antigen cross-linking of FcεRI-bound IgE is central to allergy pathogenesis. We previously demonstrated global suppression of this process by rapid desensitization with anti-FcεRIα mAbs.
OBJECTIVES
We sought to determine whether use of monovalent (mv) anti-FcεRIα mAbs increases desensitization safety without loss of efficacy.
METHODS
mv anti-human (hu) FcεRIα mAbs were produced with mouse-derived immunoglobulin variable regions and huIgG
RESULTS
mv anti-hu FcεRIα mAbs are considerably less able than divalent mAbs are to induce anaphylaxis and deplete mast cell and basophil IgE, but mv mAbs still strongly suppress IgE-mediated disease. The mv mAbs can be safely administered as a single large dose to mice with typical susceptibility to anaphylaxis, while a rapid desensitization approach safely suppresses disease in mice with increased susceptibility. Our huIgG
CONCLUSIONS
mv anti-FcεRIα mAbs more safely suppress IgE-mediated anaphylaxis and food allergy than divalent variants of the same mAbs do. These mv mAbs may be useful for suppression of huIgE-mediated disease.

Identifiants

DOI: 10.1016/j.jaci.2020.10.045 PMID: 33326804 PMC: PMC8215870
pubmed: 33326804
pii: S0091-6749(20)31729-2
doi: 10.1016/j.jaci.2020.10.045
pmc: PMC8215870
mid: NIHMS1713205
pii:
doi:

Substances chimiques

Anti-Allergic Agents 0
Antibodies, Monoclonal 0
Immunoglobulin G 0
Receptors, IgE 0
Immunoglobulin E 37341-29-0
Syk Kinase EC 2.7.10.2
Syk protein, mouse EC 2.7.10.2
Inpp5d protein, mouse EC 3.1.3.86
Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases EC 3.1.3.86

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1838-1854.e4

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK116789
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI145991
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI130103
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK078392
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI113162
Pays : United States

Informations de copyright

Copyright © 2020 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

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Auteurs

Marat V Khodoun (MV)

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Suzanne C Morris (SC)

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Wen-Hai Shao (WH)

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Crystal Potter (C)

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio.

Elizabeth Angerman (E)

Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Artem Kiselev (A)

Institute of Cytology, Russian Academy of Sciences, Saint Petersburg, Russia.

Alexander E Yarawsky (AE)

Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Andrew B Herr (AB)

Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.

Katja Klausz (K)

Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany.

Anna Otte (A)

Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany.

Matthias Peipp (M)

Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, University of Kiel, Kiel, Germany.

Fred D Finkelman (FD)

Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Division of Immunobiology, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio. Electronic address: finkelfd@ucmail.uc.edu.

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Classifications MeSH

questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Anaphylaxie › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Eucaryotes › Animaux › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antiallergiques › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps monoclonaux › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Maladies du système immunitaire › Hypersensibilité › Hypersensibilité immédiate › Hypersensibilité alimentaire › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline E › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Isotypes des immunoglobulines › Immunoglobuline G › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Mastocytes › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Lignées consanguines de souris › Souris de lignée BALB C › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › Souris transgéniques › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Phosphoric monoester hydrolases › Phosphoinositide phosphatases › Phosphatidylinositol-3,4,5-trisphosphate 5-phosphatases › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteur Fc › Récepteurs aux IgE › Suppression of IgE-mediated anaphylaxis and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Protein-tyrosine kinases › Syk kinase › Suppression of IgE-mediated anaphylaxis and...