Division of Immunopathology, Department of Pathophysiology and Allergy Research, Center for Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Austria.
Immunobiology. 2013 Jun;218(6):884-91. doi: 10.1016/j.imbio.2012.10.008. Epub 2012 Oct 26.
IgE antibody-mediated allergies affect more than 25% of the population worldwide. To investigate therapeutic and preventive effects of passive immunization with allergen-specific IgG antibodies on allergy in mouse models we used clinically relevant pollen allergens. In a treatment model, mice were sensitized to the major birch pollen allergen Bet v 1 and to the major grass pollen allergens, Phl p 1 and Phl p 5 and then received passive immunization with rabbit IgG antibodies specific for the sensitizing or an unrelated allergen. In a prevention model, mice obtained passive immunization with allergen-specific rabbit IgG before sensitization. Kinetics of the levels of administered IgG antibodies, effects of administered allergen-specific IgG on allergen-specific IgE reactivity, the development of IgE and IgG responses and on immediate allergic reactions were studied by ELISA, rat basophil leukaemia degranulation assays and skin testing, respectively. Treated mice showed an approximately 80% reduction of allergen-specific IgE binding and basophil degranulation which was associated with the levels of administered allergen-specific IgG antibodies. Preventive administration of allergen-specific IgG antibodies suppressed the development of allergen-specific IgE and IgG1 antibody responses as well as allergen-induced basophil degranulation and skin reactivity. Our results show that passive immunization with allergen-specific IgG antibodies is effective for treatment and prevention of allergy to clinically important pollen allergens in a mouse model and thus may pave the road for the clinical application of allergen-specific antibodies in humans.
IgE 抗体介导的过敏反应影响全球超过 25%的人口。为了研究过敏原特异性 IgG 抗体的被动免疫对小鼠模型中过敏的治疗和预防作用,我们使用了临床相关的花粉过敏原。在治疗模型中,小鼠被致敏于主要桦树花粉过敏原 Bet v 1 和主要草花粉过敏原 Phl p 1 和 Phl p 5,然后接受针对致敏或非相关过敏原的兔 IgG 抗体的被动免疫。在预防模型中,小鼠在致敏前获得过敏原特异性兔 IgG 的被动免疫。通过 ELISA、大鼠嗜碱性白血病脱颗粒测定和皮肤测试分别研究了给予的 IgG 抗体的动力学、给予的过敏原特异性 IgG 对过敏原特异性 IgE 反应性的影响、IgE 和 IgG 反应的发展以及即刻过敏反应。治疗小鼠显示过敏原特异性 IgE 结合和嗜碱性粒细胞脱颗粒的约 80%减少,这与给予的过敏原特异性 IgG 抗体的水平相关。过敏原特异性 IgG 抗体的预防性给药抑制了过敏原特异性 IgE 和 IgG1 抗体反应以及过敏原诱导的嗜碱性粒细胞脱颗粒和皮肤反应性的发展。我们的结果表明,过敏原特异性 IgG 抗体的被动免疫对于治疗和预防小鼠模型中临床重要花粉过敏原的过敏是有效的,因此可能为人类过敏原特异性抗体的临床应用铺平道路。