Southampton General Hospital, Southampton, UK.
Allergy. 2009 Dec;64(12):1728-36. doi: 10.1111/j.1398-9995.2009.02201.x. Epub 2009 Oct 15.
Asthma is a chronic inflammatory disease of the airways in which immunoglobulin E (IgE) plays a key role by activating a variety of inflammatory cells through interactions with FcepsilonRI and FcepsilonRII receptors. The role of IgE in allergic inflammation provided the rationale for developing omalizumab, a humanized monoclonal anti-IgE antibody, for patients with moderate-to-severe or severe allergic asthma. The reductions in circulating levels of IgE resulting from omalizumab treatment leads to reductions in FcepsilonRI expression on mast cells, basophils and dendritic cells. This combined effect results in attenuation of several markers of inflammation, including peripheral and bronchial tissue eosinophilia and levels of granulocyte macrophage colony stimulating factor, interleukin (IL)-2, IL-4, IL-5 and IL-13. By blocking IgE binding to its receptors and diminishing dendritic cell FcepsilonRI receptor expression, omalizumab may also reduce allergen presentation to T cells and the production of Th2 cytokines. The anti-inflammatory effects of omalizumab may, therefore, explain the reductions in asthma exacerbations and symptoms seen in clinical trials in patients with moderate-to-severe or severe, persistent, inadequately controlled allergic asthma.
哮喘是一种气道的慢性炎症性疾病，免疫球蛋白 E（IgE）通过与 FcepsilonRI 和 FcepsilonRII 受体相互作用激活各种炎症细胞，从而发挥关键作用。IgE 在过敏炎症中的作用为开发奥马珠单抗（omalizumab）提供了依据，奥马珠单抗是一种人源化单克隆抗 IgE 抗体，用于治疗中重度或重度过敏性哮喘患者。奥马珠单抗治疗导致 IgE 循环水平降低，从而导致肥大细胞、嗜碱性粒细胞和树突状细胞上 FcepsilonRI 表达减少。这种联合作用导致炎症的几个标志物减弱，包括外周和支气管组织嗜酸性粒细胞增多和粒细胞巨噬细胞集落刺激因子、白细胞介素（IL）-2、IL-4、IL-5 和 IL-13 的水平降低。通过阻断 IgE 与其受体的结合并减少树突状细胞 FcepsilonRI 受体表达，奥马珠单抗还可能减少过敏原向 T 细胞的呈递以及 Th2 细胞因子的产生。因此，奥马珠单抗的抗炎作用可以解释在中重度或重度、持续性、控制不佳的过敏性哮喘患者的临床试验中观察到的哮喘恶化和症状减少。
