"Auto-anti-IgE": Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation
"Auto-anti-IgE": Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation
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DOI：
10.1016/j.jaci.2014.06.029
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发表时间：
2014-12-01
影响因子：
14.2
通讯作者：
Gould, Hannah J.
中科院分区：
文献类型：
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作者：
Chan, Yih-Chih;Ramadani, Faruk;Gould, Hannah J.
背景：在哮喘和其他疾病患者中发现了天然存在的ige特异性IgG自身抗体，但其功能谱尚不清楚。目的：验证以下假设：(1)在所有受试者的血清中均可检测到IgG抗ige自身抗体，但与对照组相比，哮喘患者的血清中IgG抗ige抗体升高，而与特应性状态无关；（ii）一些激活ige敏化的嗜碱性细胞；（iii）一些抑制过敏原诱导的嗜碱性粒细胞活化。方法：采用ELISA法检测血清中ige特异性IgG自身抗体。使用嗜碱性粒细胞激活试验检测血清在存在和不存在过敏原的情况下激活IgE致敏的人血液嗜碱性粒细胞的能力，以及在稳定表达人FceRI的大鼠嗜碱性细胞系上抑制过敏原与特定IgE结合的能力。结果：在特应性和非特应性哮喘患者以及对照组中检测到结合游离IgE和Fce - ri结合IgE的IgG自身抗体。虽然一些能够激活IgE敏感的嗜碱性粒细胞，但另一些则抑制过敏原诱导的嗜碱性粒细胞激活，至少部分是通过抑制IgE与特定过敏原的结合。结论：自然产生的IgG抗ige自身抗体可能抑制或诱导嗜碱性粒细胞活化。它们的作用方式不同于治疗性IgG抗ige抗体，如omalizumab。它们至少可以部分解释为什么产生过敏原特异性IgE的特应性受试者从未出现临床症状，以及为什么奥玛单抗治疗在严重特应性哮喘中具有不同的临床益处。
Background: Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood.Objective: Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation.Methods: IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FceRI.Results: IgG autoantibodies binding to both free and Fce RI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen.Conclusion: Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma.