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抗IgE治疗

Author
Peter J Barnes, DM, DSc, FRCP, FRS
Section Editor
Bruce S Bochner, MD
Deputy Editor
Anna M Feldweg, MD

引言

免疫球蛋白E(immunoglobulin E, IgE)在包括哮喘在内的变态反应性疾病的发病机制中发挥着核心作用[1]。因此，IgE介导的免疫学途径已长期作为哮喘治疗药物的一个引人注意的靶点。

本专题将研究使用抗IgE单克隆抗体中和IgE的疗法在哮喘治疗中的应用。该生物学疗法通过阻止IgE与其受体结合而发挥中和IgE的作用。其他有前景的减少IgE的方法以及抗IgE在其他疾病中的研究性应用将简单讨论。抗IgE疗法在哮喘的整体治疗(按照国内和国际哮喘指南推荐)中的作用请参见其他专题。 (参见“哮喘管理概述”)

IgE在哮喘中的作用

当针对年龄进行调整后，大部分哮喘患者循环IgE浓度是升高的[2]。机体对常见的吸入性变应原(如来自屋内尘蟎、花粉、动物毛屑、霉菌及蟑螂的变应原)发生反应形成的特异性IgE导致了变应性致敏。

IgE是在白细胞介素(interleukin, IL)-4及密切相关的IL-13这2种细胞因子的介导下由B淋巴细胞产生。这两种细胞因子是由多种类型的细胞产生的，其中包括Th2(T-helper 2, Th2)细胞。Th2细胞是特应症中普遍存在的T辅助淋巴细胞的一个亚组[3,4]。以下两种共刺激分子的相互作用显著增加了IgE的形成：表达于Th2细胞的CD40配体和表达于B细胞的CD40。经适当刺激的B细胞成熟为浆细胞，后者分泌变应原特异性IgE，这些IgE在血液中循环并与肥大细胞、嗜碱性粒细胞和其他细胞表面的高亲和力受体(FcεRⅠ)结合。 (参见“Mast cells: Surface receptors and signal transduction”, section on ‘High affinity IgE receptor’)

肥大细胞和嗜碱性粒细胞上的这些IgE分子与蛋白质变应原交叉连接，引起这些细胞的激活，从而释放已形成的介质(如组胺)，并增加脂质介质(如前列腺素类和半胱氨酰-白三烯类)的合成[5]。肥大细胞介质的释放导致支气管收缩及血浆渗出。因此，IgE在变应性哮喘患者吸入变应原后出现速发性支气管收缩的机制中发挥着核心作用。 (参见“The biology of IgE”)

                                 

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Literature review current through: 2017-07 . | This topic last updated: 2017-07-27.
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