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奥马珠单抗对嗜碱性粒细胞的影响:哮喘和慢性自发性荨麻疹的潜在生物标志物。

Effects of omalizumab on basophils: Potential biomarkers in asthma and chronic spontaneous urticaria.

机构信息

Nazarbayev University School of Medicine, Department of Medicine, Nur-Sultan, Kazakhstan; University Medical Center, Department of Pediatrics, Nur-sultan, Kazakhstan.

Nazarbayev University School of Medicine, Department of Biomedical Sciences, Nur-Sultan, Kazakhstan.

出版信息

Cell Immunol. 2020 Dec;358:104215. doi: 10.1016/j.cellimm.2020.104215. Epub 2020 Sep 12.

Abstract

Omalizumab is an anti-IgE humanized monoclonal antibody approved for the treatment of severe asthma and chronic spontaneous urticaria. Omalizumab binds free serum IgE and antagonizes its interaction with FcεRI, which is considered the main pharmacodynamic mechanism responsible for the clinical response to the treatment. The reduction of IgE serum concentration down-regulates the cellular expression of FcεRI on basophils. However, the biological events occurring on basophils during the therapy with omalizumab are multiple and complex. Here we review the current evidence regarding the specific biological effects of omalizumab on basophils in patients with asthma and chronic spontaneous urticaria. In addition to the modulation of IgE receptors, omalizumab may affect basophils homeostasis, intra-cellular signaling, cellular responsiveness/activation and cytokine release. These effects may be partially responsible for the clinical success of omalizumab and potentially provide useful biological markers for future assessment of the clinical response to the treatment. However, further investigation is required to better elucidate the role of basophils during the treatment with omalizumab.

摘要

奥马珠单抗是一种抗 IgE 人源化单克隆抗体,已被批准用于治疗严重哮喘和慢性自发性荨麻疹。奥马珠单抗结合游离血清 IgE 并拮抗其与 FcεRI 的相互作用,这被认为是治疗反应的主要药效学机制。血清 IgE 浓度的降低下调了嗜碱性粒细胞上 FcεRI 的细胞表达。然而,奥马珠单抗治疗期间嗜碱性粒细胞上发生的生物学事件是多样且复杂的。在这里,我们回顾了关于奥马珠单抗在哮喘和慢性自发性荨麻疹患者中对嗜碱性粒细胞的具体生物学作用的现有证据。除了 IgE 受体的调节外,奥马珠单抗还可能影响嗜碱性粒细胞的稳态、细胞内信号转导、细胞反应性/激活和细胞因子释放。这些作用可能部分解释了奥马珠单抗的临床成功,并为未来评估治疗反应提供了有用的生物学标志物。然而,需要进一步的研究来更好地阐明在奥马珠单抗治疗期间嗜碱性粒细胞的作用。

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