Neutrophil Cell Population Data biomarkers for Acute Bacterial Infection

Abstract

Introduction: Cell population data (CPD) reported by Sysmex XN analyzer provide quantitative information on morphological and functional characteristics of leukocytes. We aimed to evaluate the value of CPD in the clinical decision-making in patients with fever and to assess the clinical value for the early diagnosis of acute bacterial infection, in comparison with classical markers. Methods: A total of 215 consecutive patients with fever (bacterial or viral) and 212 healthy subjects without alterations in the hemogram were studied. The analysis was performed within 24-36 h from the onset of fever. Mann-Whitney U-test and Kruskal-Wallis ANOVA were applied to detect statistical differences of group, statistically significant P < 0.05. Receiver operating characteristic (ROC) curve analysis was utilized to establish the diagnostic performance of CPDs in the diagnosis of bacterial infection in a group of patients with fever. Results: The values of neutrophil granularity intensity and neutrophil reactive intensity showed increasing values from healthy, viral, to bacterial infections. NEUT-WY was the CPD with the best performance for the diagnosis of bacterial infection. Area under curve (AUC) 0.916 (95 % confidence interval 0.883-0.942) for a cutoff >616 the sensitivity was 87.1 % and the specificity was 85.4 %. This AUC presented no differences with those of percentage of neutrophils (P = 0.4451) nor neutrophil/lymphocyte ratio (0.2769). Conclusions: NEUT-WY reflects an increase in the nucleic acid content of neutrophils in response to bacteria, and it is a reliable test for the diagnosis of acute bacterial infection and could aid in discriminating the etiology of fever.

The Detection of Neutrophil Activation by Automated Blood Cell Counter in Sepsis

“…The neutrophil parameters obtained by representative cell analyzer Sysmex XN-20 were as follows: forward scattered light (NE-FSC), side scattered light 2). Among them, variations in RNA/DNA contents represented by NE-WY and NE-SFL were reported to be significantly higher in patients with sepsis compared to the healthy controls [2][3][4] . In a population of patients at the onset of fever, NE-SFL, NE-WY, NE-WZ, and Monocytes-WZ parameters reached the highest AUC scores for predicting sepsis 5) .…”

Neutrophil Reactivity Intensity and misclassification of immature granulocytes

“…NEUT-RI corresponds to the NEUT-Y value in the Sysmex XE-series and represents the neutrophil reactivity and metabolic activity expressed by the mean fluorescent signal of the neutrophil population. 6 The parameter was proposed as an early marker of infection and sepsis, [6][7][8] a risk marker of mechanical ventilation during Coronavirus disease 2019 9,10 as well as a marker of autoimmune disease. [11][12][13] The normal level of NEUT-RI in samples without pathology was documented to be 45.4 fluorescence intensity (FI) with a standard deviation of 2.8 FI.…”

The importance of morphological changes in neutrophils in the diagnosis of bacterial infections in dogs with confirmed urinary tract infections in a Veterinary Care Service, Rio de Janeiro, Brazil

“…As for toxic PMNs, of the type with granulations, they correspond to the accumulation of the microbicidal enzyme myeloperoxidase in the phase before medullary maturation; they are usually associated with quantitative and morphological changes, observed in the leukogram/hemogram, evidenced by a specific relative and/or absolute count, by microscopy. Thus indicating the intensity and reactivity not only by counts, but mainly according to the degree of neutrophils with granulations, being proportional to infection/inflammation ( Bastos et al, 2016 ; Burton et al, 2013 ; Lilliehöök et al, 2016 ; Oliveira-Costa et al, 2022 ; Polton, 2013 ; Thrall et al, 2012 ; Urrechaga et al, 2018 ). These changes observed in the study of these cells in cystoscopy allow us to confirm, diagnose, monitor and quantify the severity of infectious and Inflammatory processes; because in general, serious infections can be observed in the consistent presence of leukocytosis with neutrophilia or not, and nevertheless, morphological changes in neutrophils, mainly toxic granulations, Döhle bodies, toxic vacuolizations, target neutrophils and karyorrhexis, were always present in patients with bacterial infections associated with changes in circulating immature granulocytes according to the increased risk of death ( Bastos et al, 2016 ; Lilliehöök et al, 2016 ; Papasouliotis & Murphy, 2021 ; Polton, 2013 ; Thrall et al, 2012 ; Vidya et al, 2021 ; Weiss & Wardrop, 2011 ), as the potential for bacterial toxemia reflects a medullary effect on neutrophilopoiesis with increased nucleic acid content in the cytoplasm of PMNs in response to bacterial infections ( Oliveira-Costa et al, 2022 ; Urrechaga et al, 2018 ).…”

“…Thus indicating the intensity and reactivity not only by counts, but mainly according to the degree of neutrophils with granulations, being proportional to infection/inflammation ( Bastos et al, 2016 ; Burton et al, 2013 ; Lilliehöök et al, 2016 ; Oliveira-Costa et al, 2022 ; Polton, 2013 ; Thrall et al, 2012 ; Urrechaga et al, 2018 ). These changes observed in the study of these cells in cystoscopy allow us to confirm, diagnose, monitor and quantify the severity of infectious and Inflammatory processes; because in general, serious infections can be observed in the consistent presence of leukocytosis with neutrophilia or not, and nevertheless, morphological changes in neutrophils, mainly toxic granulations, Döhle bodies, toxic vacuolizations, target neutrophils and karyorrhexis, were always present in patients with bacterial infections associated with changes in circulating immature granulocytes according to the increased risk of death ( Bastos et al, 2016 ; Lilliehöök et al, 2016 ; Papasouliotis & Murphy, 2021 ; Polton, 2013 ; Thrall et al, 2012 ; Vidya et al, 2021 ; Weiss & Wardrop, 2011 ), as the potential for bacterial toxemia reflects a medullary effect on neutrophilopoiesis with increased nucleic acid content in the cytoplasm of PMNs in response to bacterial infections ( Oliveira-Costa et al, 2022 ; Urrechaga et al, 2018 ). The study of neutrophils and “toxic changes”, a term used for the morphological changes associated with infections or inflammatory disorders ( Gossett et al, 1985 ), bringing the importance of the neutrophil phenotype to a new focus of research on the pathology of infections and sepsis, which would potentially make the diagnosis and monitoring of these pathologies more reliable ( Ellett et al, 2018 ; Paolino & Williams, 2021 ; Troìa et al, 2017 ), thus seeking a more sensitive examination and the recognition of any morphological variations and, therefore, evidence of functional status, in response to stimuli such as infections ( Mayadas et al, 2014 ; Paolino & Williams, 2021 ; Urrechaga et al, 2018 ).…”