Department of Medicine, University of Virginia Health, Charlottesville, Virginia; Department of Microbiology, University of Virginia Health, Charlottesville, Virginia.
Department of Pediatrics, University of Virginia Health, Charlottesville, Virginia.
Ann Allergy Asthma Immunol. 2023 May;130(5):617-621.e1. doi: 10.1016/j.anai.2023.01.024. Epub 2023 Feb 2.
There is increasing recognition of a type 2 (T2) inflammatory pattern in a subset of patients with chronic obstructive pulmonary disease (COPD) or emphysema, characterized by blood and airway eosinophilia. The mechanism underlying this is not well established. The recognition that CD125 (interleukin [IL]-5 receptor alpha) is expressed on some lung neutrophils and eosinophils in patients with asthma led us to speculate that CD125 may also be expressed on lung neutrophils in patients with COPD or emphysema.
To interrogate the expression of CD125 on lung neutrophils (and, when present, eosinophils) in patients with COPD/emphysema and identify a meaningful biomarker to predict neutrophil CD125 expression, including other markers of T2 inflammation.
We obtained blood and bronchoalveolar lavage (BAL) samples from patients with physician-diagnosed COPD/emphysema undergoing a clinically indicated bronchoscopy.
We found that a highly variable percentage of BAL neutrophils indeed expressed surface CD125 (0%-78.7%), with obvious clustering of CD125 and CD125 patterns. No correlation was found with clinical characteristics, blood or BAL eosinophil or neutrophil counts, BAL cytokines, or BAL eosinophil CD125 expression.
We conclude that, similar to asthma, lung neutrophils from patients with COPD display interleukin-5 receptor alpha (CD125) on their surface. This along with the frequent presence of IL-4 and IL-5 in airway fluid further suggests a possible role of the T2 pathway in contributing to COPD severity.
ClinicalTrials.gov Identifier: NCT03984799.
越来越多的人认识到,慢性阻塞性肺疾病(COPD)或肺气肿患者亚群存在 2 型(T2)炎症模式,其特征是血液和气道嗜酸性粒细胞增多。其发病机制尚未明确。我们注意到,CD125(白细胞介素[IL]-5 受体α)在哮喘患者的一些肺中性粒细胞和嗜酸性粒细胞上表达,由此推测 CD125 也可能在 COPD 或肺气肿患者的肺中性粒细胞上表达。
检测 COPD/肺气肿患者肺中性粒细胞(以及存在时的嗜酸性粒细胞)上 CD125 的表达,并确定一个有意义的生物标志物来预测中性粒细胞 CD125 的表达,包括 T2 炎症的其他标志物。
我们从经临床指示支气管镜检查的诊断为 COPD/肺气肿的患者中获得了血液和支气管肺泡灌洗液(BAL)样本。
我们发现 BAL 中性粒细胞表面确实存在高度可变比例的 CD125(0%-78.7%),CD125 及其模式明显聚类。未发现与临床特征、血液或 BAL 嗜酸性粒细胞或中性粒细胞计数、BAL 细胞因子或 BAL 嗜酸性粒细胞 CD125 表达相关。
我们得出结论,与哮喘相似,COPD 患者的肺中性粒细胞表面存在白细胞介素-5 受体α(CD125)。气道液中经常存在 IL-4 和 IL-5 进一步表明 T2 途径可能在 COPD 严重程度中发挥作用。
ClinicalTrials.gov 标识符:NCT03984799。