Precision Medicine, Oncology R&D, AstraZeneca, Cambridge, United Kingdom.
COPD/IPF Bioscience, Research and Early Development, Respiratory & Immunology, Biopharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden.
PLoS One. 2021 Feb 10;16(2):e0246627. doi: 10.1371/journal.pone.0246627. eCollection 2021.
There is a growing body of evidence for the utility of eosinophil-derived neurotoxin (EDN) as a biomarker in asthma, including association with eosinophilic airway inflammation, assessment of disease severity and potential for predicting pathogenic risks, including exacerbations. However, to interpret any biomarker data with confidence, it is first important to understand the preanalytical factors and biological variation that may affect its reliable measurement and results interpretation. In this study we defined the healthy serum EDN reference range for men and women as 1.98 to 26.10 ng/mL, with no significant gender differences. Smoking did not impact the mean EDN levels and no circadian rhythm was identified for EDN, unlike blood eosinophils (EOS) where levels peaked at 00:00h. EDN expression in different cell types was investigated and shown to occur primarily in eosinophils, indicating they are likely to be the main cellular repository for EDN. We also confirm that the quantification of serum EDN is not influenced by the type of storage tube used, and it is stable at ambient temperature or when refrigerated for at least 7 days and for up to one year when frozen at -20°C or -80°C. In summary, EDN is a stable biomarker that may prove useful in precision medicine approaches by enabling the identification of a subpopulation of asthma patients with activated eosinophils and a more severe form of the disease.
越来越多的证据表明,嗜酸性粒细胞衍生神经毒素(EDN)作为哮喘的生物标志物具有实用性,包括与嗜酸性气道炎症相关,评估疾病严重程度和预测潜在的致病风险,包括恶化。然而,为了有信心地解释任何生物标志物数据,首先重要的是要了解可能影响其可靠测量和结果解释的分析前因素和生物学变异。在这项研究中,我们将男性和女性的健康血清 EDN 参考范围定义为 1.98 至 26.10ng/ml,无显著性别差异。吸烟不会影响 EDN 的平均水平,也没有发现 EDN 的昼夜节律,而血液嗜酸性粒细胞(EOS)的水平在 00:00h 达到峰值。研究了不同细胞类型的 EDN 表达情况,结果表明 EDN 主要存在于嗜酸性粒细胞中,表明它们可能是 EDN 的主要细胞储存库。我们还证实,血清 EDN 的定量不受所用储存管类型的影响,在环境温度下或冷藏至少 7 天时稳定,在-20°C 或-80°C 冷冻时稳定至少一年。总之,EDN 是一种稳定的生物标志物,通过识别具有激活嗜酸性粒细胞和更严重疾病形式的哮喘患者亚群,可能在精准医学方法中证明是有用的。