Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies
Long-term tolerance after allergen immunotherapy is accompanied by selective persistence of blocking antibodies
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DOI：
10.1016/j.jaci.2010.12.1080
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发表时间：
2011-02-01
影响因子：
14.2
通讯作者：
Durham, Stephen R.
中科院分区：
文献类型：
--
作者：
James, Louisa K.;Shamji, Mohamed H.;Durham, Stephen R.
背景：草花粉免疫治疗变应性鼻炎是一种改善疾病的治疗方法，其结果是在治疗停止后持续数年的长期临床耐受性。积极治疗与产生能够阻断过敏原- ige相互作用的草花粉特异性抑制IgG抗体有关。目的：我们试图研究停止草花粉免疫治疗后igg相关抑制抗体与长期临床耐受性的关系。方法：我们进行了一项为期4年的研究，对中重度变应性鼻炎患者进行了随机、双盲、安慰剂对照的皮下草花粉免疫治疗停药。所有受试者接受草花粉免疫治疗注射2年（n = 13），随后再接受活性（n = 57）或安慰剂（n = 6）注射2年。临床结果包括季节性症状和抢救药物的使用。在基线、2年和4年后采集血清标本，定量测定过敏原特异性IgG抗体。在细胞实验中，通过流式细胞术和共聚焦显微镜检测ige草花粉过敏原复合物与B细胞的结合，检测血清中igg对ige过敏原结合的抑制生物活性。结果：停药2年后，临床改善保持不变。虽然免疫治疗诱导的草花粉特异性IgG1和IgG4水平在停药期间下降到接近免疫治疗前的水平，但过敏原特异性IgG抗体的抑制生物活性保持不变。结论：草花粉免疫治疗诱导了一种对IgE具有强抑制活性的过敏原特异性IgG抗体亚群，这种抗体在停药后仍然存在，这可能是长期临床耐受的原因。[J] .中华过敏症杂志，2011;27:591 - 591。
Background: Grass pollen immunotherapy for allergic rhinitis is a disease-modifying treatment that results in long-term clinical tolerance lasting years after treatment discontinuation. Active treatment is associated with generation of inhibitory grass pollen-specific IgG antibodies capable of blocking allergen-IgE interactions.Objectives: We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy.Methods: We conducted a 4-year study in which patients who had moderate-to-severe allergic rhinitis underwent a randomized, double-blind, placebo-controlled discontinuation of subcutaneous grass pollen immunotherapy. All subjects received grass pollen immunotherapy injections for 2 years (n = 13), followed by a further 2 years of either active (n 5 7) or placebo (n = 6) injections. Clinical outcomes included seasonal symptoms and use of rescue medication. Serum specimens were collected at baseline and after 2 and 4 years for quantification of allergen-specific IgG antibodies. Sera were also tested for IgG-dependent inhibitory bioactivity against IgE-allergen binding in cellular assays by using flow cytometry and confocal microscopy to detect binding of IgE-grass pollen allergen complexes to B cells.Results: Clinical improvement was maintained after 2 years of discontinuation. Although immunotherapy-induced grass pollen-specific IgG1 and IgG4 levels decreased to near-preimmunotherapy levels during discontinuation, inhibitory bioactivity of allergen-specific IgG antibodies was maintained unchanged.Conclusion: Grass pollen immunotherapy induces a subpopulation of allergen-specific IgG antibodies with potent inhibitory activity against IgE that persists after treatment discontinuation and that could account for long-term clinical tolerance. (J Allergy Clin Immunol 2011;127:509-16.)