Abstract
IntroductionRecent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. The origin of cf-DNA is unclear.MethodsTotal plasma cf-DNA was quantified directly in plasma and the amplifiable cf-DNA assessed using quantitative PCR in 132 patients with bacteremia caused by Staphylococcus aureus, Streptococcus pneumoniae, ß-hemolytic streptococcae or Escherichia coli. The quality of cf-DNA was analyzed with a DNA Chip assay performed on 8 survivors and 8 nonsurvivors. Values were measured on days 1–4 after positive blood culture, on day 5–17 and on recovery.ResultsThe maximum cf-DNA values on days 1–4 (n = 132) were markedly higher in nonsurvivors compared to survivors (2.03 vs 1.26 ug/ml, p<0.001) and the AUCROC in the prediction of case fatality was 0.81 (95% CI 0.69–0.94). cf-DNA at a cut-off level of 1.52 ug/ml showed 83% sensitivity and 79% specificity for fatal disease. High cf-DNA (>1.52 ug/ml) remained an independent risk factor for case fatality in a logistic regression model. Qualitative analysis of cf-DNA showed that cf-DNA displayed a predominating low-molecular-weight cf-DNA band (150–200 bp) in nonsurvivors, corresponding to the size of the apoptotic nucleosomal DNA. cf-DNA concentration showed a significant positive correlation with visually graded apoptotic band intensity (R = 0.822, p<0.001).ConclusionsPlasma cf-DNA concentration proved to be a specific independent prognostic biomarker in bacteremia. cf-DNA displayed a predominating low-molecular-weight cf-DNA band in nonsurvivors corresponding to the size of apoptotic nucleosomal DNA.
Highlights
Recent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis
The results show that plasma cell free DNA is elevated in bacteremic patients with poor outcome
Cf-DNA and outcome of bacteremia Median cell free DNA (cf-DNA) values were significantly higher in nonsurvivors compared to survivors on days 3 (1.97 vs 1.20 ug/ml, p,0.001)
Summary
Recent studies have shown that apoptosis plays a critical role in the pathogenesis of sepsis. High plasma cell free DNA (cf-DNA) concentrations have been shown to be associated with sepsis outcome. There are significant gaps in our knowledge regarding the basic pathophysiological mechanisms associated with fatal outcome. This hampers attempts to develop novel therapeutic interventions for this condition. Several studies indicate that most deaths from bacteremia and sepsis are the result of a substantially impaired immune response due to the extensive death of immune system cells [1]. Studies during recent years have shown that immunosupression plays a pivotal role in severe sepsis [2,3].
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