Department of Respiratory Medicine, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, Japan.
Research Institute for Diseases of Old Ages, Juntendo University Faculty of Medicine and Graduate School of Medicine, Tokyo 113-8421, Japan.
Biomolecules. 2023 Mar 15;13(3):538. doi: 10.3390/biom13030538.
Benralizumab treatment reduces exacerbations and improves symptom control and quality of life in patients with severe eosinophilic asthma. However, the determination of biomarkers that predict therapeutic effectiveness is required for precision medicine. Herein, we elucidated the dynamics of various parameters before and after treatment as well as patient characteristics predictive of clinical effectiveness after 1 year of benralizumab treatment in severe asthma in a real-world setting. Thirty-six patients with severe asthma were treated with benralizumab for 1 year. Lymphocyte subsets in peripheral blood samples were analyzed using flow cytometry. Treatment effectiveness was determined based on the ACT score, forced expiratory volume in 1 s (FEV1), and the number of exacerbations. Benralizumab provided symptomatic improvement in severe asthma. Benralizumab significantly decreased peripheral blood eosinophil and basophil counts and the frequencies of regulatory T cells (Tregs), and increased the frequencies of Th2 cells. To our knowledge, this is the first study to show benralizumab treatment increasing circulating Th2 cells and decreasing circulating Tregs. Finally, the ROC curve to discriminate patients who achieved clinical effectiveness of benralizumab treatment revealed that the frequency of circulating Th17 cells and FeNO levels might be used as parameters for predicting the real-world response of benralizumab treatment in patients with severe asthma.
贝那鲁肽治疗可减少重度嗜酸性粒细胞性哮喘患者的恶化次数，改善症状控制和生活质量。然而，需要确定预测治疗效果的生物标志物，以实现精准医疗。在此，我们在真实环境中阐明了重度哮喘患者接受贝那鲁肽治疗 1 年后，治疗前后各种参数的动态变化以及预测临床疗效的患者特征。36 例重度哮喘患者接受贝那鲁肽治疗 1 年。采用流式细胞术分析外周血样本中的淋巴细胞亚群。根据 ACT 评分、FEV1 和恶化次数来确定治疗效果。贝那鲁肽为重度哮喘提供了症状改善。贝那鲁肽显著降低了外周血嗜酸性粒细胞和嗜碱性粒细胞计数以及调节性 T 细胞（Tregs）的频率，并增加了 Th2 细胞的频率。据我们所知，这是第一项表明贝那鲁肽治疗增加循环 Th2 细胞并减少循环 Tregs 的研究。最后，区分贝那鲁肽治疗临床疗效的患者的 ROC 曲线表明，循环 Th17 细胞的频率和 FeNO 水平可能可作为预测重度哮喘患者贝那鲁肽治疗真实世界反应的参数。
