Rapid polyclonal desensitization with antibodies to IgE and Fc[epsilon]RI[alpha]

• Published in: Journal of allergy and clinical immunology Vol. 131; no. 6; pp. 1555 - 1564.e7
• Main Authors: Khodoun, Marat V, Kucuk, Zeynep Yesim, Strait, Richard T, Krishnamurthy, Durga, Janek, Kevin, Lewkowich, Ian, Morris, Suzanne C, Finkelman, Fred D
• Format: Journal Article
• Language: English
• Published: St. Louis Elsevier Limited 01.06.2013
• Subjects: Allergies; Asthma; Food allergies; Histamine
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2013.02.043

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 Fc[straight epsilon]RI. 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-Fc[straight epsilon]RI mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and Fc[straight epsilon]RI 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-Fc[straight epsilon]RI mAb that only binds Fc[straight epsilon]RI 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[straight epsilon]RI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane Fc[straight epsilon]RI. Rapid desensitization with anti-Fc[straight epsilon]RI mAb was safer and longer lasting than rapid desensitization with antigen. Conclusion A rapid desensitization approach with anti-Fc[straight epsilon]RI 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[straight epsilon]RI mAb may be able to prevent human IgE-mediated anaphylaxis.