Neutrophil and monocyte CD64 and CD163 expression in critically ill neonates and children with sepsis: comparison of fluorescence intensities and calculated indexes

Mojca Groselj-Grenc, Alojz Ihan, Metka Derganc, Mojca Groselj-Grenc, Alojz Ihan, Metka Derganc

Abstract

Objective: To evaluate the expression of CD64 and CD163 on neutrophils and monocytes in SIRS with/without sepsis and to compare the diagnostic accuracy of CD64 and CD163 molecules expression determined as (1) mean fluorescence intensities (MFI) of CD64 and CD163; and (2) the ratio (index) of linearized MFI to the fluorescence signal of standardized beads.

Patients and methods: Fifty-six critically ill neonates and children with systemic inflammatory response syndrome (SIRS) and suspected sepsis, classified into two groups: SIRS with sepsis (n = 29) and SIRS without sepsis (n = 27).

Results: CD64 and CD163 MFI measured on neutrophils and monocytes were elevated in patients with SIRS with sepsis. Diagnostic accuracy of indexes was equal to diagnostic accuracy of MFI for CD64 on neutrophils (0.833 versus 0.854 for day 0 and 0.975 versus 0.983 for day 1) and monocytes (0.811 versus 0.865 for day 0 and 0.825 versus 0.858 for day 1), and CD163 on neutrophils (0.595 versus 0.655 for day 0 and 0.677 versus 0.750 for day 1), but not for CD163 on monocytes.

Conclusion: CD64 MFI, CD163 MFI, CD64 indexes for neutrophils and monocytes, and CD163 index for neutrophils can all be used for discrimination of SIRS and sepsis in critically ill neonates and children. CD64 index for neutrophils, however, is superior to all other markers.

Figures

Figure 1
Figure 1
Gating of neutrophils, monocytes, and lymphocytes in FSC/SSC representative FACS diagrams. CD64 and CD163 histograms (colored) versus CD64 isotype controls (lined) are presented for granulocytes (red), lymphocytes (green), and monocytes (blue).
Figure 2
Figure 2
CD64 indexes for neutrophils at the time of suspected sepsis (day 0), and 24 hours later (day 1), for separate groups of neonates and children. Data are presented as box plots (median value and interquartile range). Outliers and extreme cases of index CD64 are not shown.
Figure 3
Figure 3
Receiver-operating characteristic (ROC) curves of CD64 and CD163 indexes (i) for neutrophils and monocytes for critically ill neonates and children with SIRS with sepsis and SIRS without sepsis at the time of suspected sepsis (day 0) and 24 hours later (day 1).

References

    1. Nimmerjahn F, Ravetch JV. Fcγ receptors: old friends and new family members. Immunity. 2006;24(1):19–28.
    1. Radaev S, Sun P. Recognition of immunoglobulins by Fcγ receptors. Molecular Immunology. 2002;38(14):1073–1083.
    1. Qureshi SS, Lewis SM, Gant VA, Treacher D, Davis BH, Brown KA. Increased distribution and expression of CD64 on blood polymorphonuclear cells from patients with the systemic inflammatory response syndrome (SIRS) Clinical & Experimental Immunology. 2001;125(2):258–265.
    1. Livaditi O, Kotanidou A, Psarra A, et al. Neutrophil CD64 expression and serum IL-8: sensitive early markers of severity and outcome in sepsis. Cytokine. 2006;36(5-6):283–290.
    1. Hirsh M, Mahamid E, Bashenko Y, Hirsh I, Krausz MM. Overexpression of the high-affinity Fcγ receptor (CD64) is associated with leukocyte dysfunction in sepsis. Shock. 2001;16(2):102–108.
    1. Fischer G, Schneider E, Moldawer LL, et al. CD64 surface expression on neutrophils is transiently upregulated in patients with septic shock. Intensive Care Medicine. 2001;27(12):1848–1852.
    1. Davis BH, Bigelow NC. Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis. Laboratory Hematology. 2005;11(2):137–147.
    1. Davis BH, Olsen SH, Ahmad E, Bigelow NC. Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients. Archives of Pathology and Laboratory Medicine. 2006;130(5):654–661.
    1. Ng PC, Li G, Chui KM, et al. Neutrophil CD64 is a sensitive diagnostic marker for early-onset neonatal infection. Pediatric Research. 2004;56(5):796–803.
    1. Ng PC, Li G, Chui KM, et al. Quantitative measurement of monocyte HLA-DR expression in the identification of early-onset neonatal infection. Biology of the Neonate. 2006;89(2):75–81.
    1. Ng PC, Li K, Wong RPO, Chui KM, Wong E, Fok TF. Neutrophil CD64 expression: a sensitive diagnostic marker for late-onset nosocomial infection in very low birthweight infants. Pediatric Research. 2002;51(3):296–303.
    1. Layseca-Espinosa E, Pérez-González LF, Torres-Montes A, et al. Expression of CD64 as a potential marker of neonatal sepsis. Pediatric Allergy and Immunology. 2002;13(5):319–327.
    1. Fjaertoft G, Håkansson L, Ewald U, Foucard T, Venge P. Neutrophils from term and preterm newborn infants express the high affinity Fcγ-receptor I (CD64) during bacterial infections. Pediatric Research. 1999;45(6):871–876.
    1. Fjaertoft G, Håkansson LD, Pauksens K, Sisask G, Venge P. Neutrophil CD64 (FcγRI) expression is a specific marker of bacterial infection: a study on the kinetics and the impact of major surgery. Scandinavian Journal of Infectious Diseases. 2007;39(6-7):525–535.
    1. Herra CM, Keane CT, Whelan A. Increased expression of Fcγ receptors on neutrophils and monocytes may reflect ongoing bacterial infection. Journal of Medical Microbiology. 1996;44(2):135–140.
    1. Barth E, Fischer G, Schneider EM, Wollmeyer J, Georgieff M, Weiss M. Differences in the expression of CD64 and mCD14 on polymorphonuclear cells and on monocytes in patients with septic shock. Cytokine. 2001;14(5):299–302.
    1. Kristiansen M, Graversen JH, Jacobsen C, et al. Identification of the haemoglobin scavenger receptor. Nature. 2001;409(6817):198–201.
    1. Zuwała-Jagiełło J. Haemoglobin scavenger receptor: function in relation to disease. Acta Biochimica Polonica. 2006;53(2):257–268.
    1. Davis BH, Zarev PV. Human monocyte CD163 expression inversely correlates with soluble CD163 plasma levels. Cytometry Part B: Clinical Cytometry. 2005;63(1):16–22.
    1. Hintz KA, Rassias AJ, Wardwell K, et al. Endotoxin induces rapid metalloproteinase-mediated shedding followed by up-regulation of the monocyte hemoglobin scavenger receptor CD163. Journal of Leukocyte Biology. 2002;72(4):711–717.
    1. Møller HJ, Moestrup SK, Weis N, et al. Macrophage serum markers in pneumococcal bacteremia: prediction of survival by soluble CD163. Critical Care Medicine. 2006;34(10):2561–2566.
    1. Møller HJ, Aerts H, Grønbæk H, et al. Soluble CD163: a marker molecule for monocyte/macrophage activity in disease. Scandinavian Journal of Clinical and Laboratory Investigation. 2002;62(7, supplement 237):29–33.
    1. Gaïni S, Koldkjær OG, Pedersen SS, Pedersen C, Moestrup SK, Møller HJ. Soluble haemoglobin scavenger receptor (sCD163) in patients with suspected community-acquired infections. APMIS. 2006;114(2):103–111.
    1. Proulx F, Fayon M, Farrell CA, Lacroix J, Gauthier M. Epidemiology of sepsis and multiple organ dysfunction syndrome in children. Chest. 1996;109(4):1033–1037.
    1. Davis BH. Improved diagnostic approaches to infection/sepsis detection. Expert Review of Molecular Diagnostics. 2005;5(2):193–207.
    1. Goldstein B, Giroir B, Randolph A, International Consensus Conference on Pediatric Sepsis International pediatric sepsis consensus conference: definitions for sepsis and organ dysfunction in pediatrics. Pediatric Critical Care Medicine. 2005;6(1):2–8.
    1. Zweig MH, Campbell G. Receiver-operating characteristic (ROC) plots: a fundamental evaluation tool in clinical medicine. Clinical Chemistry. 1993;39(4):561–577.
    1. Beck JR, Shultz EK. The use of relative operating characteristic (ROC) curves in test performance evaluation. Archives of Pathology and Laboratory Medicine. 1986;110(1):13–20.
    1. Nuutila J, Hohenthal U, Laitinen I, et al. Simultaneous quantitative analysis of FcγRI (CD64) expression on neutrophils and monocytes: a new, improved way to detect infections. Journal of Immunological Methods. 2007;328(1-2):189–200.
    1. Ng PC, Lam HS. Diagnostic markers for neonatal sepsis. Current Opinion in Pediatrics. 2006;18(2):125–131.
    1. Shao J, Huang XW, Sun MY, Du LZ, Tang YM, Le YL. Expression of peripheral blood neutrophil CD64 in neonatal septicaemia. Zhonghua Er Ke Za Zhi. 2005;43(7):510–513.
    1. Stakos DA, Kotsianidis I, Tziakas DN, et al. Leukocyte activation after coronary stenting in patients during the subacute phase of a previous ST-elevation myocardial infarction. Coronary Artery Disease. 2007;18(2):105–110.
    1. Schaer DJ, Schaer CA, Schoedon G, Imhof A, Kurrer MO. Hemophagocytic macrophages constitute a major compartment of heme oxygenase expression in sepsis. European Journal of Haematology. 2006;77(5):432–436.
    1. Sulahian TH, Pioli PA, Wardwell K, Guyre PM. Cross-linking of FcγR triggers shedding of the hemoglobin-haptoglobin scavenger receptor CD163. Journal of Leukocyte Biology. 2004;76(1):271–277.
    1. Timmermann M, Högger P. Oxidative stress and 8-iso-prostaglandin F2α induce ectodomain shedding of CD163 and release of tumor necrosis factor-α from human monocytes. Free Radical Biology and Medicine. 2005;39(1):98–107.
    1. Buechler C, Ritter M, Orsó E, Langmann T, Klucken J, Schmitz G. Regulation of scavenger receptor CD163 expression in human monocytes and macrophages by pro- and antiinflammatory stimuli. Journal of Leukocyte Biology. 2000;67(1):97–103.
    1. Davis B, Becker K, Rinder H, Davis K. Neutrophil CD64 expression, a marker of sepsis/infection, can be performed on a hematology blood counter and has variable correlation to C-reactive protein, procalcitonin and soluble CD163. Critical Care. 2007;11(supplement 4):p. 20.

Source: PubMed

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