We wanted to determine whether this approach can be adapted to suppress all IgE-mediated allergies in mice by injecting serially increasing doses of monoclonal antibodies (mAbs) to IgE or Fc¦ÅRI¦Á.
Active and passive models of antigen- and anti-IgE mAb-induced IgE-mediated anaphylaxis were used. Mice were desensitized with serially increasing doses of anti-IgE mAb, anti-Fc¦ÅRI¦Á mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and Fc¦ÅRI and IgE expression were evaluated.
Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-Fc¦ÅRI¦Á mAb that only binds Fc¦ÅRI that is not occupied by IgE suppressed both active and passive IgE-mediated anaphylaxis without inducing disease. It quickly, but temporarily, suppressed IgE-mediated anaphylaxis by decreasing mast cell signaling through Fc¦ÅRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane Fc¦ÅRI. Rapid desensitization with anti-Fc¦ÅRI¦Á mAb was safer and longer lasting than rapid desensitization with antigen.
A rapid desensitization approach with anti-Fc¦ÅRI¦Á mAb safely desensitizes mice to IgE-mediated anaphylaxis by inducing mast cell anergy and later removing all mast cell IgE. Rapid desensitization with an anti-human Fc¦ÅRI¦Á mAb may be able to prevent human IgE-mediated anaphylaxis.