title: Rapid polyclonal desensitization with antibodies to IgE and FcεRIα.
abstract: BACKGROUND
  Rapid desensitization, a procedure in which persons allergic to an antigen are treated at short intervals with increasing doses of that antigen until they tolerate a large dose, is an effective, but risky, way to induce temporary tolerance.
  
  
  OBJECTIVE
  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 FcεRIα.
  
  
  METHODS
  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-FcεRIα mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and FcεRI and IgE expression were evaluated.
  
  
  RESULTS
  Rapid desensitization with anti-IgE mAb suppressed IgE-mediated immediate hypersensitivity; however, some mice developed mild anaphylaxis during desensitization. Rapid desensitization with anti-FcεRIα mAb that only binds FcεRI 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 FcεRI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane FcεRI. Rapid desensitization with anti-FcεRIα mAb was safer and longer lasting than rapid desensitization with antigen.
  
  
  CONCLUSIONS
  A rapid desensitization approach with anti-FcεRIα 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 FcεRIα mAb may be able to prevent human IgE-mediated anaphylaxis.
authors: Department of Research, Cincinnati Veterans Affairs Medical Center, Cincinnati, Ohio, USA.
authors: Marat V
authors: MV
authors: Khodoun
authors: Zeynep Yesim
authors: ZY
authors: Kucuk
authors: Richard T
authors: RT
authors: Strait
authors: Durga
authors: D
authors: Krishnamurthy
authors: Kevin
authors: K
authors: Janek
authors: Ian
authors: I
authors: Lewkowich
authors: Suzanne C
authors: SC
authors: Morris
authors: Fred D
authors: FD
authors: Finkelman
mesh_terms: D000707:Anaphylaxis / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000276:immunology*; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D000941:Antigens / Q000276:immunology; D001491:Basophils / Q000276:immunology / Q000378:metabolism; D001667:Binding, Competitive / Q000276:immunology; D003888:Desensitization, Immunologic; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy; D007073:Immunoglobulin E / Q000276:immunology* / Q000378:metabolism; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011485:Protein Binding / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology* / Q000378:metabolism
chemical_list: D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D000941:Antigens; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D007073:Immunoglobulin E
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