Haldar Koirobi, Mistry Vijay, Richardson Mathew, Hamblet Corinne, Jison Maria, Barer Michael R, McCrae Christopher, Brightling Christopher E
Institute for Lung Health, NIHR, BRC, Department of Respiratory Sciences, College of Life Sciences, University of Leicester, Leicester, UK.
Translational Science and Experimental Medicine, Early Respiratory and Immunology, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
ERJ Open Res. 2025 Apr 7;11(2). doi: 10.1183/23120541.00802-2024. eCollection 2025 Mar.
One-third of patients with COPD have an eosinophilic inflammatory phenotype. Benralizumab is an afucosylated humanised monoclonal antibody that targets the interleukin-5 receptor α subunit, leading to rapid and near-complete eosinophil depletion antibody-dependent cellular cytotoxicity. We hypothesised that benralizumab-targeted immune modulation could have an impact on the airway microbiome in COPD. The objective of the present study was to investigate the effect of benralizumab treatment on inflammation and the sputum microbiome in COPD.
Sputum samples from 94 COPD patients enrolled to the GALATHEA trial (NCT02138916) and randomised to receive placebo (33), benralizumab at 100 mg (29) or 30 mg (32) over 52 weeks were analysed at baseline, week 24 and at end of treatment (week 56). Sputum microbiota taxonomic profiles and diversity indices, generated from paired-end Illumina sequencing targeting the 16S rRNA gene, were used for comparative analyses. Linear mixed model analyses were applied to blood and sputum cell counts and eosinophil mediators for within- and between-treatment group analyses.
Participants treated with 100 and 30 mg benralizumab, respectively, showed a significant reduction from baseline in both blood and sputum eosinophil counts (blood: p=1.2e-10 and p=8.8e-10; sputum p=0.03 and p=0.004) and eosinophil-derived serum mediators (eosinophil cationic protein: p<3e-09 and p<2e-08; eosinophil-derived neurotoxin: p<8e-12 and p<2e-09). No significant changes in the composition or diversity of the sputum microbiome were observed.
In this study, the airway microbiome measured in sputum was unaffected by a targeted reduction of eosinophilic inflammation with benralizumab treatment.
三分之一的慢性阻塞性肺疾病（COPD）患者具有嗜酸性粒细胞炎症表型。贝那利珠单抗是一种去岩藻糖基化的人源化单克隆抗体，可靶向白细胞介素-5受体α亚基，通过抗体依赖性细胞毒性作用导致嗜酸性粒细胞迅速且近乎完全耗竭。我们推测，贝那利珠单抗靶向的免疫调节可能会对COPD患者的气道微生物群产生影响。本研究的目的是调查贝那利珠单抗治疗对COPD患者炎症和痰液微生物群的影响。
对参加GALATHEA试验（NCT02138916）并随机接受安慰剂（33例）、100mg贝那利珠单抗（共29例）或30mg贝那利珠单抗（共32例）治疗52周的94例COPD患者的痰液样本，在基线、第24周和治疗结束时（第56周）进行分析。通过针对16S rRNA基因的双端Illumina测序生成痰液微生物群分类学图谱和多样性指数，用于比较分析。采用线性混合模型分析对血液和痰液细胞计数以及嗜酸性粒细胞介质进行组内和组间分析。
分别接受100mg和30mg贝那利珠单抗治疗的参与者，血液和痰液中的嗜酸性粒细胞计数均较基线显著降低（血液：p = 1.2×10⁻¹⁰和p = 8.8×10⁻¹⁰；痰液：p = 0.03和p = 0.004），且嗜酸性粒细胞衍生的血清介质也显著降低（嗜酸性粒细胞阳离子蛋白：p < 3×10⁻⁹和p < 2×10⁻⁸；嗜酸性粒细胞衍生的神经毒素：p < 8×10⁻¹²和p < 2×10⁻⁹）。未观察到痰液微生物群的组成或多样性有显著变化。
在本研究中，通过贝那利珠单抗治疗靶向降低嗜酸性粒细胞炎症，未影响痰液中检测到的气道微生物群。
