Mepolizumab depletes inflammatory but preserves homeostatic eosinophils in severe asthma

IF 12.6 1区医学 Q1 ALLERGY

Allergy Pub Date : 2024-08-08 DOI:10.1111/all.16267

Michael Fricker, John Harrington, Sarah A. Hiles, Peter G. Gibson

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Abstract

Background

Eosinophils are key therapeutic targets in severe asthma that are suppressed by IL5 (mepolizumab) and IL5 receptor (benralizumab) blockade. The effect of IL5 pathway biologics on recently described homeostatic (hEOs) and inflammatory (iEOs) eosinophil subsets is unknown. We aimed to determine the relative impact of mepolizumab and benralizumab treatment on eosinophil subset and phenotype, and explore clinical associations of eosinophil subsets with severe asthma characteristics and treatment response.

Methods

We performed a cross-sectional observational study of severe asthma (eosinophilic n = 32, non-eosinophilic n = 23, mepolizumab-treated n = 25), with longitudinal follow-up of 30 eosinophilic participants at two timepoints (4–24 weeks, >24 weeks) post-commencement of mepolizumab (n = 20) or benralizumab (n = 10). Blood hEOs and iEOs were measured by flow cytometry assessment of surface CD62L protein.

Results

iEO proportion was significantly lower in mepolizumab-treated participants in both the cross-sectional and longitudinal study. Mepolizumab and benralizumab depleted iEOs to a similar extent, however a significantly greater number of hEOs remained in mepolizumab participants at follow-up. Greater iEO proportion correlated with poorer asthma control in eosinophilic but not non-eosinophilic asthma. Higher residual iEO proportion correlated with poorer asthma control in mepolizumab-treated individuals. Reduced blood eosinophil viability was observed in around half of mepolizumab-treated participants, which was associated with significantly better asthma control and spirometry.

Conclusions

Mepolizumab depletes iEOs and reduces circulating eosinophil viability in severe asthma but preserves a residual population of circulatory hEOs. In contrast benralizumab depleted both iEOs and hEOs. Higher iEO abundance and eosinophil viability are associated with poorer clinical outcomes following mepolizumab-treatment. Monitoring circulating eosinophil phenotype and viability may be useful to predict biologic treatment response in severe asthma.

Abstract Image

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美泊利珠单抗可消耗重症哮喘患者的炎性嗜酸性粒细胞，但保留稳态嗜酸性粒细胞。

背景：嗜酸性粒细胞是严重哮喘的关键治疗靶点，IL5（mepolizumab）和IL5受体（benralizumab）阻断剂可抑制嗜酸性粒细胞。IL5通路生物制剂对最近描述的静态（hEOs）和炎症（iEOs）嗜酸性粒细胞亚群的影响尚不清楚。我们旨在确定mepolizumab和benralizumab治疗对嗜酸性粒细胞亚群和表型的相对影响，并探讨嗜酸性粒细胞亚群与严重哮喘特征和治疗反应的临床关联：我们进行了一项重症哮喘横断面观察研究（嗜酸性粒细胞患者 n = 32，非嗜酸性粒细胞患者 n = 23，甲泼尼单抗治疗患者 n = 25），并在甲泼尼单抗（n = 20）或苯拉利珠单抗（n = 10）开始治疗后的两个时间点（4-24 周，>24 周）对 30 名嗜酸性粒细胞患者进行了纵向随访。通过流式细胞术评估表面CD62L蛋白，测量血液中的hEO和iEO。美泊利珠单抗和苯拉利珠单抗对iEO的消耗程度相似，但在随访中，美泊利珠单抗参与者中仍有更多的hEO。在嗜酸性粒细胞性哮喘中，较高的iEO比例与较差的哮喘控制率相关，但与非嗜酸性粒细胞性哮喘无关。残留的iEO比例越高，mepolizumab治疗者的哮喘控制效果越差。约半数接受过美泊珠单抗治疗的患者血液中的嗜酸性粒细胞存活率降低，这与哮喘控制率和肺活量显著改善有关：结论：在严重哮喘患者中，美泊利珠单抗会消耗iEOs并降低循环中嗜酸性粒细胞的活力，但会保留循环中残余的hEOs。相比之下，苯拉利珠单抗会同时消耗iEO和hEO。较高的iEO丰度和嗜酸性粒细胞活力与mepolizumab治疗后较差的临床结果有关。监测循环中嗜酸性粒细胞的表型和活力可能有助于预测重症哮喘的生物治疗反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Allergy 医学-过敏

CiteScore

26.10

自引率

9.70%

发文量

393

审稿时长

2 months

期刊介绍： Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.