Comparison of neutrophil CD64 and monocytic HLA-DR with existing biomarkers for the diagnosis and prognosis of sepsis

Pandey, K. K.; Malviya, Deepak; Awasthi, Namrata P; Nath, Soumya Sankar; Harjai, Mamta

doi:10.5114/ait.2021.108579

Cited by 9 publications

(6 citation statements)

References 29 publications

(44 reference statements)

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“…Changes on the molecular and protein level that might contribute to an impaired function of the immune system, such as cell surface expression of HLA-DR on monocytes (mHLA-DR), were not evaluated in the present study. Downregulation of mHLA-DR is an established marker for monocyte suppression and disease severity in sepsis 50 , 51 and has been reported to correlate with disease severity in COVID-19 52 , 53 . However, mHLA-DR levels in this present COVID-19 patient cohort were comparable to healthy controls in previous investigations 9 , further underlining the functionality of their monocytes.…”

Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 pneumonia and bacterial pneumonia patients differ in a second hit immune response model

Moser

Feuerecker

Biere

et al. 2022

Sci Rep

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Secondary infections have been shown to complicate the clinical course and worsen the outcome of critically ill patients. Severe Coronavirus Disease 2019 (COVID-19) may be accompanied by a pronounced cytokine release, and immune competence of these patients towards most pathogenic antigens remains uncompromised early in the disease. Patients with bacterial sepsis also exhibit excessive cytokine release with systemic hyper-inflammation, however, typically followed by an anti-inflammatory phase, causing immune paralysis. In a second hit immune response model, leukocyte activation capacity of severely ill patients with pneumonia caused by SARS-CoV-2 or by bacteria were compared upon ICU admission and at days 4 and 7 of the ICU stay. Blood cell count and release of the pro-inflammatory cytokines IL-2, IFNγ and TNF were assessed after whole-blood incubation with the potent immune stimulus pokeweed mitogen (PWM). For comparison, patients with bacterial sepsis not originating from pneumonia, and healthy volunteers were included. Lymphopenia and granulocytosis were less pronounced in COVID-19 patients compared to bacterial sepsis patients. After PWM stimulation, COVID-19 patients showed a reduced release of IFNγ, while IL-2 levels were found similar and TNF levels were increased compared to healthy controls. Interestingly, concentrations of all three cytokines were significantly higher in samples from COVID-19 patients compared to samples from patients with bacterial infection. This fundamental difference in immune competence during a second hit between COVID-19 and sepsis patients may have implications for the selection of immune suppressive or enhancing therapies in personalized medicine.

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Section: Discussionmentioning

confidence: 99%

SARS-CoV-2 pneumonia and bacterial pneumonia patients differ in a second hit immune response model

Moser

Feuerecker

Biere

et al. 2022

Sci Rep

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“…These immune cells are often the primary factors responsible for the development of sepsis (Rimmelé et al 2016 ; Boomer et al 2011 ). Monitoring the expression of HLA-DR can aid in the diagnosis, prognosis, and prediction of sepsis (Zhuang et al 2017 ; Kyriazopoulou and Giamarellos-Bourboulis 2021 ; Yoshida 2004 ; Pandey et al 2021 ; Xu et al 2020 ; Boeddha et al 2018 ; Lelubre et al 2017 ). Two studies published in 2022 also examined the relationship and mechanism associated with the expression of HLA family proteins and sepsis (Horn et al 2022 ; Wu et al 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Use of machine learning-based integration to develop a monocyte differentiation-related signature for improving prognosis in patients with sepsis

Ning

Sun

Wang

et al. 2023

Mol Med

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Background Although significant advances have been made in intensive care medicine and antibacterial treatment, sepsis is still a common disease with high mortality. The condition of sepsis patients changes rapidly, and each hour of delay in the administration of appropriate antibiotic treatment can lead to a 4–7% increase in fatality. Therefore, early diagnosis and intervention may help improve the prognosis of patients with sepsis. Methods We obtained single-cell sequencing data from 12 patients. This included 14,622 cells from four patients with bacterial infectious sepsis and eight patients with sepsis admitted to the ICU for other various reasons. Monocyte differentiation trajectories were analyzed using the “monocle” software, and differentiation-related genes were identified. Based on the expression of differentiation-related genes, 99 machine-learning combinations of prognostic signatures were obtained, and risk scores were calculated for all patients. The “scissor” software was used to associate high-risk and low-risk patients with individual cells. The “cellchat” software was used to demonstrate the regulatory relationships between high-risk and low-risk cells in a cellular communication network. The diagnostic value and prognostic predictive value of Enah/Vasp-like (EVL) were determined. Clinical validation of the results was performed with 40 samples. The “CBNplot” software based on Bayesian network inference was used to construct EVL regulatory networks. Results We systematically analyzed three cell states during monocyte differentiation. The differential analysis identified 166 monocyte differentiation-related genes. Among the 99 machine-learning combinations of prognostic signatures constructed, the Lasso + CoxBoost signature with 17 genes showed the best prognostic prediction performance. The highest percentage of high-risk cells was found in state one. Cell communication analysis demonstrated regulatory networks between high-risk and low-risk cell subpopulations and other immune cells. We then determined the diagnostic and prognostic value of EVL stabilization in multiple external datasets. Experiments with clinical samples demonstrated the accuracy of this analysis. Finally, Bayesian network inference revealed potential network mechanisms of EVL regulation. Conclusions Monocyte differentiation-related prognostic signatures based on the Lasso + CoxBoost combination were able to accurately predict the prognostic status of patients with sepsis. In addition, low EVL expression was associated with poor prognosis in sepsis.

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“…Data analysis was performed using the BD FACS Diva software version 6.1.3. This process has been validated elsewhere [ 26 , 27 , 28 ]. All laboratory tests were performed at the standardized Laboratory Department of CRH.…”

Section: Methodsmentioning

confidence: 99%

Diagnostic Value of Neutrophil CD64 in Sepsis Patients in the Intensive Care Unit: A Cross-Sectional Study

et al. 2023

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Little is known about the role of neutrophil CD64 (nCD64) in detecting sepsis early in Asian populations. We examined the cut-off and predictive values of nCD64 for diagnosing sepsis in Vietnamese intensive care units (ICU) patients. A cross-sectional study was conducted at the ICU of Cho Ray Hospital between January 2019 and April 2020. All 104 newly admitted patients were included. Sensitivity (Sens), specificity (Spec), positive and negative predictive values (PPV and NPV), and receiver operating characteristic (ROC) curves were calculated to compare the diagnostic values of nCD64 with those of procalcitonin (PCT) and white blood cell (WBC) for sepsis. The median nCD64 value in sepsis patients was statistically higher than that of non-sepsis patients (3106 [1970–5200] vs. 745 [458–906] molecules/cell, p < 0.001). ROC analysis found that the AUC value of nCD64 was 0.92, which was higher than that of PCT (0.872), WBC (0.637), and nCD64 combined, with WBC (0.906) and nCD64 combined with WBC and PCT (0.919), but lower than that of nCD64 combined with PCT (0.924). With an AUC value of 0.92, the nCD64 index of 1311 molecules/cell-detected sepsis with 89.9% Sens, 85.7% Spec, 92.5% PPV, and 81.1% NPV. nCD64 can be a useful marker for early sepsis diagnosis in ICU patients. nCD64 combined with PCT may improve the diagnostic accuracy.

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Comparison of neutrophil CD64 and monocytic HLA-DR with existing biomarkers for the diagnosis and prognosis of sepsis

Cited by 9 publications

References 29 publications

SARS-CoV-2 pneumonia and bacterial pneumonia patients differ in a second hit immune response model

SARS-CoV-2 pneumonia and bacterial pneumonia patients differ in a second hit immune response model

Use of machine learning-based integration to develop a monocyte differentiation-related signature for improving prognosis in patients with sepsis

Diagnostic Value of Neutrophil CD64 in Sepsis Patients in the Intensive Care Unit: A Cross-Sectional Study

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