Article

Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis. Lab Hematol

Trillium Diagnostics, LLC, Scarborough, Maine, USA.
Laboratory Hematology 02/2005; 11(2):137-47. DOI: 10.1532/LH96.04077
Source: PubMed

ABSTRACT There is a clear need for improved indicators of infection or sepsis to increase the sensitivity and specificity of both diagnosis and therapeutic monitoring. One of the effects of inflammatory cytokines on the innate immune response is the rapid up-regulation of CD64 expression on the neutrophil membrane. We and others have hypothesized that the measurement of neutrophil CD64 expression might represent an improved diagnostic indicator of infection and sepsis. In this study we assessed the relative ability of flow cytometric neutrophil CD64 measurements, neutrophil counts, myeloid immaturity differential counts, and flagging on an automated hematology analyzer to correlate with the presence of infection, as determined by a retrospective clinical scoring system of infection or sepsis. A total of 160 blood samples were randomly selected to derive equal proportions of the 3 categories of flags on a Coulter STKS blood counter that indicate the presence of a myeloid left shift. The patients for these samples were scored by retrospective chart review and placed into 4 groups on the basis of likelihood of infection, sepsis, or severe tissue injury. Neutrophil CD64 expression demonstrated a superior sensitivity (94.1%), specificity (84.9%), and positive predictive likelihood ratio (6.24), compared with neutrophil counts (sensitivity, 79.4%; specificity, 46.8%; positive predictive likelihood ratio, 1.49), band counts (sensitivity, 87.5%; specificity, 43.5%; positive predictive likelihood ratio, 1.55), myeloid immaturity fraction (sensitivity, 94.6%; specificity, 84.5%; positive predictive likelihood ratio, 2.12), and flagging on an automated hematology analyzer (sensitivity, 94.1%; specificity, 40.5%; positive predictive likelihood ratio, 1.58). Relative to the other laboratory parameters, the neutrophil CD64 parameter also provided the best separation of the 4 clinical groups. The findings indicate that neutrophil CD64 expression as determined by quantitative flow cytometry is an improved diagnostic indicator of infection/sepsis relative to current laboratory indicators of relative or absolute myeloid cell counts or hematology analyzer flagging algorithms.

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    • "CD64 is a high-affinity and restricted isotype-specificity FcγRI receptor expressed on macrophages, monocytes, neutrophils , and eosinophils [1] [2]. There are several reports regarding its potential utility for the diagnostic assessment of sepsis or infection in adults [3] [4] [5] [6] [7] [8] and neonates [9] [10] [11] [12], but only a few in children [13] [14]. In an adult study, a higher intensity of CD64 expression has been found on neutrophils from patients with systemic inflammatory response syndrome (SIRS) and sepsis than on neutrophils from patients with SIRS only [3]. "
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    ABSTRACT: 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. 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). 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. 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.
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    ABSTRACT: Background and aim. Neonatal sepsis is a signiicant contributor to morbidity and mortality globally. Blood culture is the most reliable method for detection of bacterial infection. However, its sensitivity is low and its use in the diagnosis of bacteraemia is fraught with diiculties. CD64 antigen is up-regulated in neutrophils only when they are activated, and has been shown to be a potential biomarker for infection. e primary objective of this study was quantitation of neutrophil CD64 by ow cytometry in neonates with signs and symptoms suggestive of sepsis/infection in the rst 4 weeks of life. Methods and results. In this prospective observational study, patients were classiied into categories of infection, namely deenite, probable and possible. Of 76 neonates, 1 had deenite infection, 5 probable infection, 30 possible infection, and 32 no infection. e neutrophil CD64 index at a cut-oo value of 1.8 had a high negative predictive value (95.2%) in ruling out combined probable and deenite infection. Conclusions. We recommend inclusion of the neutrophil CD64 index into the diagnostic algorithm for neonatal sepsis, as it has a high negative predictive value and can be used to rule out infection. As the positive predictive value of the index was low in connrming infection, it should be used as a screening rather than a connrmatory test. S Afr J CH 2013;7(1):25-29. DOI:10.7196/SAJCH.482
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    ABSTRACT: Riassunto La sepsi è costituita dalla reazione sistemica acuta dell'organismo ospite all'infezione. I gradi di gravità e gli stadi di malattia in cui questa sindrome si pre-senta sono caratterizzati da numerosi e diversi segni e sintomi clinici e di laboratorio che, sfortunatamen-te, non esprimono completa specificità. Nell'organi-smo, l'infezione è caratterizzata da eventi che coin-volgono cellule (monociti, macrofagi, neutrofili), e fattori umorali (citochine, markers di reattività, anti-corpi, fattori della coagulazione e di attivazione del complemento, ecc.); il grado dei cambiamenti di que-sti elementi, in termini di espressione di molecole di attivazione, rilascio di sostanze reattive e modula-zione della risposta dell'organismo, dipende da una serie di variabili quali i diversi agenti patogeni, la suscettibilità genetica individuale, l'immunodeficien-za, i fattori concomitanti, ecc. Nel passato recente poche sono state, in laboratorio, le reali novità ri-guardanti gli indicatori diagnostici di sepsi, nonostan-te i notevoli progressi avvenuti nella comprensione dei meccanismi molecolari e della biologia di cellule e citochine interessate nel processo della risposta immune dell'ospite, e non risultano al momento di-sponibili in questo campo markers che posseggano la sensibilità e specificità necessaria a scopi diagno-stici in tempi rapidi. La recentemente introduzione di test genetici per tracciare la regolazione dei geni che governano la risposta immune e di biologia mo-lecolare per la ricerca veloce multipla degli agenti eziologici che sostengono l'infezione, sembra poter apportare, in un prossimo futuro, nuovi contributi di laboratorio vantaggiosi per la diagnostica clinica. Tuttavia, ancora oggi, trattamenti inadeguati, risul-tato di ritardi nella diagnosi, continuano a gravare sulla prognosi degli stati settici. Per le sue caratteri-stiche peculiari, l'esame emocromocitometrico e la formula leucocitaria sembrano poter fornire risultati utili nel raggiungimento di outcome clinici positivi in tempi utili nella sepsi. Nel presente studio si valu-ta il valore diagnostico di parametri vecchi e nuovi dell'emocromo in diversi pazienti settici e si discuto-no le caratteristiche necessarie per un contributo tem-pestivo del test alla diagnosi e al follow up terapeuti-co della patologia. In particolare si propongono per-corsi analitici che, costruiti con diversi dati ematolo-gici e informazioni complementari fornite in modo rapido da differenti tecnologie, propongono una va-lutazione complessiva di conteggi, misure, morfolo-gia e funzionalità cellulare.
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