Rapid polyclonal desensitization with antibodies to IgE and FcεRIα
Rapid polyclonal desensitization with antibodies to IgE and FcεRIα
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DOI：
10.1016/j.jaci.2013.02.043
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发表时间：
2013-06-01
影响因子：
14.2
通讯作者：
Finkelman, Fred D.
中科院分区：
文献类型：
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作者：
Khodoun, Marat V.;Kucuk, Zeynep Yesim;Finkelman, Fred D.
背景：快速脱敏是指对某一抗原过敏的人进行短时间间隔的治疗，不断增加该抗原的剂量，直到他们对大剂量的抗原耐受，这是一种有效但有风险的诱导暂时性耐受的方法。目的：我们想要确定这种方法是否适用于通过连续递增剂量的抗IgE或Fc epsilon RIα的单抗来抑制所有由IgE介导的过敏反应。用连续递增剂量的抗IgE单抗、抗Fc epsilon RIα单抗或抗原使小鼠脱敏。结果：抗IgE单抗快速脱敏可抑制IgE介导的即刻超敏反应，但部分小鼠在脱敏过程中出现轻度过敏反应。用抗Fc epsilon RIαmAb快速脱敏，只与不被IgE占据的Fc epsilon RI结合，可抑制主动和被动的IgE介导的过敏反应，而不会诱发疾病。它通过Fc epsilon RI减少肥大细胞信号转导，从而迅速但短暂地抑制IgE介导的过敏反应，然后通过去除膜Fc epsilon RI而缓慢地诱导更持久的肥大细胞无反应。用抗Fc epsilon RIαmAb快速脱敏比用抗原快速脱敏更安全、持续时间更长。结论：抗Fc epsilon RIαmAb通过诱导肥大细胞无反应，然后清除所有肥大细胞IgE，安全地使小鼠对IgE介导的过敏反应脱敏。用抗人Fc epsilon RIα单抗快速脱敏可能能够预防人IgE介导的过敏反应。
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 epsilon RI alpha.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 epsilon RI alpha mAb, or antigen. Development of shock (hypothermia), histamine and mast cell protease release, cytokine secretion, calcium flux, and changes in cell number and Fc 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 epsilon RI alpha mAb that only binds Fc 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 epsilon RI, then slowly induced longer lasting mast cell unresponsiveness by removing membrane Fc epsilon RI. Rapid desensitization with anti-Fc epsilon RI alpha mAb was safer and longer lasting than rapid desensitization with antigen.Conclusion: A rapid desensitization approach with anti-Fc epsilon RI alpha 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 epsilon RI alpha mAb may be able to prevent human IgE-mediated anaphylaxis.