Sepsis, affecting millions of individuals annually with an associated high mortality rate, is among the top 10 causes of death. In addition, improvements in diagnostic tests for detecting and monitoring sepsis and infection have been limited in the last 25 years. Neutrophil CD64 expression has been proposed as an improved diagnostic test for the evaluation of infection and sepsis.
To evaluate the diagnostic performance of a quantitative flow cytometric assay for leukocyte CD64 expression in comparison with the standard tests for infection/sepsis in an ambulatory care setting.
Prospective analysis of 100 blood samples from patients from an emergency department setting in a 965-bed tertiary care suburban community hospital was performed for neutrophil CD64 expression, C-reactive protein, erythrocyte sedimentation rate, and complete blood count. The laboratory findings were compared with a clinical score for the likelihood of infection/sepsis, which was obtained by a blinded retrospective chart review.
The diagnostic performance, as gauged by the clinical score, varied with neutrophil CD64 (sensitivity 87.9%, specificity 71.2%, efficiency 76.8%) and outperformed C-reactive protein (sensitivity 88.2%, specificity 59.4%, efficiency 69.4%), absolute neutrophil count (sensitivity 60.0%, specificity 50.8%, efficiency 53.8%), myeloid left shift (sensitivity 68.2%, specificity 76.3%, efficiency 73.3%), and sedimentation rate (sensitivity 50.0%, specificity 65.5%, efficiency 61.0%).
Neutrophil CD64 expression quantitation provides improved diagnostic detection of infection/sepsis compared with the standard diagnostic tests used in current medical practice.
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"Besides infection, especially sepsis  , three preleukemic and/or possibly clonal disorders warrant closer attention, namely large granular lymphocyte increases in a context of neutropenia or anemia [3, 4] , hypereosinophilia syndromes  , and disorders of the glycosylphosphatidylinositol (GPI) insertion of surface molecules associated with paroxysmal nocturnal hemoglobinuria (PNH) or other disorders  . Immediate hypersensitivity can be explored in functional assays demonstrating basophil degranulation . "
[Show abstract][Hide abstract]ABSTRACT: Multiparameter flow cytometry (MFC) has become an integral part of the diagnosis and classification of hematological malignancies. However, several nonmalignant or premalignant disorders may benefit from this technology in hematology laboratories. This review provides information on the normal immunophenotypic characteristics of peripheral blood leukocyte subsets and their modifications in several clinical conditions. The usefulness of MFC and the specific markers that can be investigated in hyperlymphocytosis, infection, hypereosinophilia, paroxysmal nocturnal hemoglobinuria, and large granular lymphocyte disorders is described. Mention is also made of the developments of MFC for analyses of red blood cells or platelets.
Full-text · Article · Nov 2015 · International journal of laboratory hematology
"Elevated monocyte CD64 expression was reported in adult patients with sepsis  and in a mixed group of neonates and children with SIRS and sepsis . Neutrophil CD64 (nCD64) expression has been found to be a better diagnostic marker for sepsis than procalcitonin (PCT)  and C-reactive protein (CRP)  in adults and recently in children . An increase in the expression of integrins of the beta 2 subfamily on neutrophils, in particular CD11b, is also considered to be a good marker of cell activation . "
[Show abstract][Hide abstract]ABSTRACT: Background
Critical illness constitutes a serious derangement of metabolism. The aim of our study was to compare acute phase metabolic patterns in children with sepsis (S) or severe sepsis/septic shock (SS) to those with severe traumatic brain injury (TBI) and healthy controls (C) and to evaluate their relations to neutrophil, lymphocyte and monocyte expressions of CD64 and CD11b.
Sixty children were enrolled in the study. Forty-five children with systemic inflammatory response syndrome (SIRS) were classified into three groups: TBI (n = 15), S (n = 15), and SS (n = 15). C consisted of 15 non- SIRS patients undergoing screening tests for minor elective surgery. Blood samples were collected within 6 hours after admission for flow cytometry of neutrophil, lymphocyte and monocyte expression of CD64 and CD11b (n = 60). Procalcitonin (PCT), C-reactive protein (CRP), glucose, triglycerides (TG), total cholesterol (TC), high (HDL) or low-density-lipoproteins (LDL) were also determined in all groups, and repeated on day 2 and 3 in the 3 SIRS groups (n = 150).
CRP, PCT and TG (p < 0.01) were significantly increased in S and SS compared to TBI and C; glucose did not differ among critically ill groups. Significantly lower were the levels of TC, LDL, and HDL in septic groups compared to C and to moderate changes in TBI (p < 0.0001) but only LDL differed between S and SS (p < 0.02). Among septic patients, PCT levels declined significantly (p < 0.02) with time, followed by parallel decrease of HDL (p < 0.03) and increase of TG (p < 0.02) in the SS group. Neutrophil CD64 (nCD64) expression was higher in patients with SS (81.2%) and S (78.8%) as compared to those with TBI (5.5%) or C (0.9%, p < 0.0001). nCD64 was positively related with CRP, PCT, glucose, and TG (p < 0.01) and negatively with TC, LDL, and HDL (p < 0.0001), but not with severity of illness, hematologic indices, length of stay or mechanical ventilation duration.
In sepsis, the early stress-metabolic pattern is characterized by a high (nCD64, glucose, TG) - low (TC, HDL, LDL) combination in contrast to the moderate pattern of TBI in which only glucose increases combined with a moderate cholesterol - lipoprotein decrease. These early metabolic patterns persist the first 3 days of acute illness and are associated with the acute phase CD64 expression on neutrophils.
"In antibodies, the Fab region opsonizes the antigen, and the Fc region is a ligand for the Fc receptor, presented as FcRIII on the quiescent polymorphonuclear leukocyte surface . Upon activation of neutrophils, or during apoptosis, FcRIII is released from the cell surface by proteolytic cleavage, and the enzyme responsible for this process is probably a membrane-bound metalloprotease released from granules . "
[Show abstract][Hide abstract]ABSTRACT: Neutrophils have an impressive array of microbicidal weapons, and in the presence of a pathogen, progress from a quiescent state in the bloodstream to a completely activated state. Failure to regulate this activation, for example, when the blood is flooded with cytokines after severe trauma, causes inappropriate neutrophil activation that paradoxically, is associated with tissue and organ damage. Acidic proteomic maps of quiescent human neutrophils were analyzed and compared to those of activated neutrophils from severe trauma patients. The analysis revealed 114 spots whose measured volumes differed between activated and quiescent neutrophils, with 27 upregulated and 87 downregulated in trauma conditions. Among the identified proteins, grancalcin, S100-A9 and CACNB2 reinforce observed correlations between motility and ion flux, ANXA3, SNAP, FGD1 and Zfyve19 are involved in vesicular transport and exocytosis, and GSTP1, HSPA1 HSPA1L, MAOB, UCH-L5, and PPA1 presented evidence that activated neutrophils may have diminished protection against oxidative damage and are prone to apoptosis. These are discussed, along with proteins involved in cytoskeleton reorganization, reactive oxygen species production, and ion flux. Proteins such as Zfyve19, MAOB and albumin- like protein were described for the first time in the neutrophil. In this work we achieved the identification of several proteins potentially involved in inflammatory signaling after trauma, as well as proteins described for the first time in neutrophils.
Full-text · Article · Apr 2012 · Protein and Peptide Letters