Division of Allergy and Immunology, Department of Pediatrics, Children’s Hospital of Philadelphia
Institute for Immunology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA
Curr Opin Allergy Clin Immunol. 2020 Apr;20(2):329. doi: 10.1097/ACI.0000000000000617.
The purpose of this review is to provide a brief discussion on the differential diagnosis for peripheral eosinophilia. We will then focus on targeted immunotherapies for atopic disease, their effects on absolute peripheral eosinophil counts, and use of peripheral eosinophils as a predictor of treatment response.
In atopic disease, lower absolute peripheral eosinophil counts are typically associated with improved outcomes. Much of the current evidence on eosinophils as a biomarker comes from post-hoc analyses in therapeutic immunotherapy. While changes in eosinophilia were not the primary outcome of interest in many studies, some patterns did emerge. Cytolytic mAbs AK002 and benralizumab completely reduce peripheral and tissue eosinophil numbers. Dupilumab may have paradoxical transient eosinophilia despite observed clinical efficacy.
Atopic inflammation is complex largely due to the various cytokines which affect eosinophils activation, proliferation, differentiation, and survival. This demonstrates the challenges of using peripheral eosinophilia alone as a biomarker for atopic disease activity. More attention should spotlight how different immunotherapy modalities affect eosinophil-driven responses.
本文旨在简要讨论外周血嗜酸性粒细胞增多的鉴别诊断。然后，我们将重点介绍特应性疾病的靶向免疫疗法、它们对外周血嗜酸性粒细胞绝对值的影响，以及外周血嗜酸性粒细胞作为治疗反应预测因子的作用。
在特应性疾病中，外周血嗜酸性粒细胞绝对值较低通常与更好的预后相关。目前关于嗜酸性粒细胞作为生物标志物的大部分证据来自于治疗性免疫疗法的事后分析。虽然在许多研究中，嗜酸性粒细胞的变化不是主要关注的终点，但确实出现了一些模式。细胞溶解单克隆抗体 AK002 和 benralizumab 可完全减少外周血和组织中的嗜酸性粒细胞数量。尽管观察到临床疗效，但 dupilumab 可能会出现反常的短暂嗜酸性粒细胞增多。
特应性炎症很复杂，主要是因为各种细胞因子影响嗜酸性粒细胞的激活、增殖、分化和存活。这表明仅以外周血嗜酸性粒细胞增多作为特应性疾病活动的生物标志物存在挑战。应该更多地关注不同免疫治疗模式如何影响嗜酸性粒细胞驱动的反应。
