Diagnostic and prognostic value of neutrophil extracellular traps in sepsis and their correlation with inflammatory factors
摘要
To investigate the plasma levels of neutrophil extracellular traps (NETs) biomarkers myeloperoxidase (MPO) and citrullinated histone H3 (CitH3) in sepsis patients, and to analyze their diagnostic value for sepsis, prognostic value for 28-day mortality, and correlation with inflammatory factors and organ function.
MethodsA total of 126 sepsis patients (divided into sepsis, severe sepsis and septic shock groups) and 60 healthy controls were enrolled. Sepsis patients were further divided into survival group and non-survival group according to 28-day prognosis. Plasma levels of MPO, CitH3, inflammatory factors (IL-6, IL-10, TNF-α, CXCL8) and clinical routine biomarkers (procalcitonin, PCT; lactate) were detected. Spearman correlation was used to analyze the relationship between NETs biomarkers and inflammatory factors, organ function indicators. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic efficacy of MPO and CitH3 for sepsis and their predictive value for 28-day mortality. Multivariate logistic regression was performed to identify independent predictors of 28-day mortality.
ResultsCompared with healthy controls, plasma MPO, CitH3, IL-6, TNF-α, CXCL8 and PCT levels in sepsis patients were significantly increased, while IL-10 level was significantly decreased (all P < 0.001). MPO and CitH3 levels gradually increased with the aggravation of sepsis severity (septic shock > severe sepsis > sepsis, all P < 0.05). MPO and CitH3 were positively correlated with pro-inflammatory factors (IL-6, TNF-α, CXCL8), PCT and lactate, and negatively correlated with anti-inflammatory factor IL-10 (all P < 0.001). The levels of MPO and CitH3 in non-survival group were significantly higher than those in survival group (P < 0.001). ROC analysis showed that the area under curve (AUC) of MPO and CitH3 for sepsis diagnosis was 0.842 and 0.876, respectively, and the combined detection of MPO+CitH3 had a higher AUC of 0.931 (sensitivity 87.3%, specificity 93.3%). For 28-day mortality prediction, MPO+CitH3 achieved an AUC of 0.915, which was significantly higher than that of single index and PCT+lactate (P < 0.05).Multivariate logistic regression identified CitH3 (OR = 2.84, 95% CI: 1.62–4.98, P < 0.001), MPO (OR = 1.78, 95% CI: 1.21–2.62, P = 0.003), SOFA score (OR = 1.45, 95% CI: 1.12–1.88, P = 0.005), and lactate (OR = 1.32, 95% CI: 1.05–1.66, P = 0.018) as independent predictors of 28-day mortality.
ConclusionPlasma MPO and CitH3 are highly expressed in sepsis patients, which are closely related to the severity of inflammation, organ dysfunction and short-term prognosis. Combined detection of MPO and CitH3 has high diagnostic value for sepsis and excellent prognostic efficacy for 28-day mortality, which can be used as potential biomarkers for clinical diagnosis, severity assessment and prognosis evaluation of sepsis.