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High-Content Immunophenotyping and Hierarchical Clustering Reveal Sources of Heterogeneity and New Surface Markers of Human Blood Monocyte Subsets

J. Hoffmann, K. Fišer, C. Liebetrau, N. Staubach, D. Kost, S. Voss, AZ. Heiden, O. Dörr, C. Lipps, HM. Nef, H. Möllmann, CW. Hamm, T. Keller, C. Troidl,

. 2020 ; 120 (1) : 141-155. [pub] 20191230

Jazyk angličtina Země Německo

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc20025331

Grantová podpora
Ministry of Health of the Czech Republic NV18-08-00385
Ministry of Education, Youth and Sports NPU I LO1604

OBJECTIVE:  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. RATIONALE:  In this study, we sought to investigate the immunophenome of circulating human monocyte subsets. METHODS:  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 (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults. RESULTS:  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. CONCLUSION:  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.

Citace poskytuje Crossref.org

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$a OBJECTIVE:  Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving. RATIONALE:  In this study, we sought to investigate the immunophenome of circulating human monocyte subsets. METHODS:  Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14++CD16-), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults. RESULTS:  Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification. CONCLUSION:  These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders.
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$a Möllmann, Helge $u Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. Department of Cardiology, St.-Johannes-Hospital Dortmund, Dortmund, Germany.
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$a Hamm, Christian W $u German Center for Cardiovascular Research (DZHK), Partner site Rhine-Main, Frankfurt am Main, Germany. Department of Cardiology, Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany. Division of Cardiology, Department of Internal Medicine I, University Hospital Giessen and Marburg, Giessen, Germany.
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