Allergen-specific immunotherapy with recombinant grass pollen allergens

Allergen-specific immunotherapy with recombinant grass pollen allergens
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DOI:
10.1016/j.jaci.2005.06.004
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发表时间:
2005-09-01
影响因子:
14.2
通讯作者:
Cromwell, O
Cromwell, O
中科院分区:
医学1区
文献类型:
--
作者:
Jutel, M;Jaeger, L;Cromwell, O

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背景:过敏原特异性免疫疗法使用天然来源材料的水提取物作为制剂的基础,以降低过敏反应。重组DNA技术使多种变应原的克隆成为可能,从而促进了旨在提高免疫治疗有效性和安全性的研究。目的:确定5种重组草花粉变应原混合物在减轻草花粉过敏患者症状和对症用药需求方面的有效性。方法:采用随机、双盲、安慰剂对照的方法,对伴有或不伴有哮喘的过敏性鼻结膜炎患者进行皮下注射免疫治疗。主要终点是根据单独的症状和用药分数编制的症状用药分数。次要终点包括鼻炎生活质量问卷、结膜刺激和特异性抗体反应。结果:与安慰剂相比,接受重组变应原的受试者症状药物评分显著改善,症状和药物使用均减少。鼻炎生活质量问卷在总体评估和7个独立领域中的5个领域显示出临床相关的显著改善,结膜刺激显示出有利于积极治疗的明显趋势。所有接受治疗的受试者都出现了强烈的过敏原特异性抗体(1)和抗体(4)。结论:重组变应原疫苗是改善变应性鼻炎症状的一种安全有效的治疗方法。临床上的益处与通过促进免疫球蛋白G(4)和减少免疫球蛋白E抗体而改变特异性免疫反应有关,这与诱导产生IL-10的调节性T细胞相一致。
Background: Allergen-specific immunotherapy uses aqueous extracts of natural source materials as a basis for preparations to downregulate the allergic response. Recombinant DNA technology has enabled the cloning of many allergens, thus facilitating investigations aimed at improving efficacy and safety of immunotherapy.Objective: To determine the effectiveness of a mixture of 5 recombinant grass pollen allergens in reducing symptoms and need for symptomatic medication in patients allergic to grass pollen.Methods: A randomized, double-blind, placebo-controlled study of subcutaneous injection immunotherapy was performed in subjects with allergic rhinoconjunctivitis, with or without asthma. Primary endpoint was a symptom medication score compiled from separate symptom and medication scores. Secondary endpoints included a rhinitis quality of life questionnaire, conjunctival provocation, and specific antibody responses.Results: The symptom medication score showed significant improvements in subjects receiving recombinant allergens as opposed to placebo, with reductions in both symptoms and medication usage. The rhinitis quality of life questionnaire revealed clinically relevant significant improvements in overall assessment and in 5 of 7 separate domains, and conjunctival provocation showed a clear trend in favor of active treatment. All treated subjects developed strong allergen-specific IgG(1) and IgG(4) antibody responses. Some patients were not sensitized to Phl p 5 but nevertheless developed strong IgG antibody responses to that allergen.Conclusion: A recombinant allergen vaccine can be a effective and safe treatment to ameliorate symptoms of allergic rhinitis. The clinical benefit is associated with modification of the specific immune response with promotion of IgG(4) and reduction of IgE antibodies consistent with the induction of IL-10-producing regulatory T cells.