Department of Medicine III, Cardiology, Goethe University Hospital, Frankfurt am Main, Germany.
German Center for Cardiovascular Research (DZHK), Partner site Rhine-Main, Frankfurt am Main, Germany.
Thromb Haemost. 2020 Jan;120(1):141-155. doi: 10.1055/s-0039-1700871. Epub 2019 Dec 30.
Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving.
In this study, we sought to investigate the immunophenome of circulating human monocyte subsets.
Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14CD16), intermediate (CD14CD16), and nonclassical (CD14CD16) monocytes in healthy adults.
Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification.
These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders.
血液单核细胞亚群正在成为心血管炎症的生物标志物。然而，我们对人类单核细胞异质性及其在健康和炎症状态下的免疫表型特征的理解仍在不断发展。
在这项研究中，我们试图研究循环人单核细胞亚群的免疫表型。
使用多重、高通量流式细胞术筛选阵列和计算数据分析来分析健康成年人循环经典（CD14CD16）、中间（CD14CD16）和非经典（CD14CD16）单核细胞上 242 种特定表面标志物的表达和层次关系。
使用广义线性模型和层次聚类分析，我们选择并聚类了最能可靠地区分单核细胞亚群的表位。我们验证了现有的转录谱数据，并揭示了潜在的新表面标志物，这些标志物可独特定义经典（例如，BLTR1、CD35、CD38、CD49e、CD89、CD96）、中间（例如，CD39、CD275、CD305、CDw328）和非经典（例如，CD29、CD132）亚群。此外，我们的分析还揭示了由树突状标记物 CMRF-44 和 CMRF-56 识别的表型细胞簇，与传统单核细胞分类无关。
这些结果揭示了一种临床应用的多重筛选阵列的进步，这可能有助于单核细胞亚群的特征描述和基于细胞术的生物标志物在各种炎症性疾病中的选择。
