Allergy and Clinical Immunology, National Heart and Lung Institute, Imperial College London, part of the Medical Research Council and Asthma UK Centre for Allergic Mechanisms of Asthma, UK.
J Allergy Clin Immunol. 2011 Feb;127(2):509-516.e1-5. doi: 10.1016/j.jaci.2010.12.1080.
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.
We sought to investigate the involvement of IgG-associated inhibitory antibodies with long-term clinical tolerance after discontinuation of grass pollen immunotherapy.
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 = 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.
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.
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.
过敏性鼻炎的草花粉免疫疗法是一种疾病修正治疗，可在治疗停止后持续多年产生长期临床耐受。主动治疗与产生抑制性草花粉特异性 IgG 抗体有关，这些抗体能够阻断过敏原-IgE 相互作用。
我们旨在研究在停止草花粉免疫疗法后，与长期临床耐受相关的 IgG 相关抑制性抗体。
我们进行了一项为期 4 年的研究，其中患有中重度过敏性鼻炎的患者接受了皮下草花粉免疫疗法的随机、双盲、安慰剂对照停药。所有患者均接受了 2 年的草花粉免疫疗法注射（n = 13），随后进行了 2 年的主动治疗（n = 7）或安慰剂治疗（n = 6）。临床结局包括季节性症状和急救药物的使用。在基线、2 年和 4 年后采集血清标本，用于定量测定过敏原特异性 IgG 抗体。还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 细胞结合，检测血清 IgG 依赖性抑制生物活性对 IgE-过敏原结合的抑制作用。
停药 2 年后临床改善得以维持。尽管免疫治疗诱导的草花粉特异性 IgG1 和 IgG4 水平在停药期间降至接近预免疫治疗水平，但过敏原特异性 IgG 抗体的抑制生物活性保持不变。
草花粉免疫疗法诱导了一种具有强大抑制 IgE 活性的过敏原特异性 IgG 亚群抗体，该抗体在治疗停止后持续存在，并可能导致长期临床耐受。
