Rapid polyclonal desensitization with antibodies to IgE and Fc¦ÅRI¦Á

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• 作者：Marat V. Khodoun ; PhD^a ; ^b ; Zeynep Yesim Kucuk ; MD^c ; Richard T. Strait^d ; Durga Krishnamurthy ; MS^a ; ^b ; ^&lowast ; ; Kevin Janek ; BS^b ; Ian Lewkowich ; PhD^e ; Suzanne C. Morris ; PhD^a ; ^b ; Fred D. Finkelman ; MD^b ; ^e ; ^f ; ^{finkelfd@ucmail.uc.edu}
• 关键词：Anaphylaxis ; basophils ; IgE ; Fc¦ÅRI ; mast cells ; mouse ; rapid desensitization
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2013
• 出版时间：June, 2013
• 年：2013
• 卷：131
• 期：6
• 页码：1555-1564.e7
• 全文大小：1839 K

文摘

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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¦ÅRI¦Á.

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¦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.

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¦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.

Conclusion

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.