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Zawada, A.M.* ; Fell, L.H.* ; Untersteller, K.* ; Seiler, S.* ; Rogacev, K.S.* ; Fliser, D.* ; Ziegler-Heitbrock, L. ; Heine, G.H.*

Comparison of two different strategies for human monocyte subsets gating within the large-scale prospective CARE FOR HOMe Study.

Cytometry A 87, 750-758 (2015)
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Open Access Green as soon as Postprint is submitted to ZB.
Monocytes are heterogeneous cells consisting of (at least) three subsets: classical, intermediate, and nonclassical monocytes. Correct enumeration of cell counts necessitates well-defined gating strategies, which are essentially based upon CD14 and CD16 expression. For the delineation of intermediate from nonclassical monocytes, a "rectangular gating (RG) strategy" and a "trapezoid gating (TG) strategy" have been proposed. We compared the two gating strategies in a well-defined clinical cohort of patients with chronic kidney disease (CKD). Within the ongoing CARE FOR HOMe study, monocyte subsets were reanalyzed in 416 CKD patients, who were followed 3.6 ± 1.6 years for the occurrence of a cardiovascular event. Gating was performed by either RG or TG. We analyzed the expression of surface markers, and compared the predictive role of cell counts of monocyte subsets, as defined by RG and TG, respectively. With both gating strategies, higher intermediate monocyte counts predicted the cardiovascular endpoint in Kaplan-Meier analyses (P < 0.001 with RG; P < 0.001 with TG). After correction for confounders, intermediate monocyte counts remained independent predictors in Cox-Regression analyses (HR = 1.013 [95% CI: 1.006-1.020; P < 0.001] with RG; HR = 1.015 [95% CI: 1.006-1.024; P = 0.001] with TG). NRI was 3.9% when reclassifying patients from quartiles of intermediate monocyte counts with RG strategy toward quartiles of intermediate monocytes counts with TG strategy. In expression analysis, those monocytes which are defined as intermediate monocytes by the RG strategy and as nonclassical monocytes by the TG strategy share characteristics of both subsets. In conclusion, intermediate monocytes were independent predictors of cardiovascular outcome irrespective of the applied gating strategy. Future studies should aim to identify markers that allow for an unequivocal definition of intermediate monocytes, which may further improve their power to predict cardiovascular events.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Cardiovascular Disease ; Cd14 ; Cd16 ; Chronic Kidney Disease ; Gating Strategy ; Monocytes; Predict Cardiovascular Events; Chronic Kidney-disease; Cd14(++)cd16(+) Monocytes; Cd14++cd16+ Monocytes; Dendritic Cells; Atherosclerosis; Identification; Blood; Subpopulation; Heterogeneity
ISSN (print) / ISBN 1552-4922
e-ISSN 1552-4930
Quellenangaben Volume: 87, Issue: 8, Pages: 750-758 Article Number: , Supplement: ,
Publisher Wiley
Publishing Place Hoboken, NJ
Reviewing status Peer reviewed