Treating cat allergy with monoclonal IgG antibodies that bind allergen and prevent IgE engagement

Nat Commun. 2018 Apr 12;9(1):1421. doi: 10.1038/s41467-018-03636-8.

Abstract

Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous. Next, using two potent, pre-selected allergen-blocking monoclonal IgG antibodies against the immunodominant cat allergen Fel d 1, we demonstrate that increasing the IgG/IgE ratio reduces the allergic response in mice and in cat-allergic patients: a single dose of blocking IgG reduces clinical symptoms in response to nasal provocation (ANCOVA, p = 0.0003), with a magnitude observed at day 8 similar to that reported with years of conventional SIT. This study suggests that simply augmenting the blocking IgG/IgE ratio may reverse allergy.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Allergens / administration & dosage
  • Allergens / immunology
  • Allergens / isolation & purification
  • Animal Fur / chemistry
  • Animal Fur / immunology
  • Animals
  • Antibodies, Monoclonal / biosynthesis
  • Antibodies, Monoclonal / pharmacology*
  • Binding, Competitive
  • Cats
  • Complex Mixtures / chemistry
  • Complex Mixtures / immunology
  • Desensitization, Immunologic / methods*
  • Disease Models, Animal
  • Female
  • Glycoproteins / administration & dosage
  • Glycoproteins / immunology*
  • Glycoproteins / isolation & purification
  • Humans
  • Hypersensitivity / immunology
  • Hypersensitivity / physiopathology
  • Hypersensitivity / therapy*
  • Immunoglobulin E / chemistry
  • Immunoglobulin E / immunology
  • Immunoglobulin E / metabolism
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin G / pharmacology*
  • Male
  • Mice
  • Middle Aged
  • Protein Binding / drug effects
  • Receptors, IgE / chemistry
  • Receptors, IgE / immunology*
  • Receptors, IgE / metabolism

Substances

  • Allergens
  • Antibodies, Monoclonal
  • Complex Mixtures
  • Glycoproteins
  • Immunoglobulin G
  • Receptors, IgE
  • Immunoglobulin E
  • Fel d 1 protein, Felis domesticus