Neutrophil-derived circulating free DNA (cf-DNA/NETs), a potential prognostic marker for mortality in patients with severe burn injury

Abstract

The predictive value of circulating free DNA/neutrophil extracellular traps (cf-DNA/NETs) has recently been shown in patients with major trauma for sepsis, multiple organ failure, and mortality. Here we report on the predictive potential of cf-DNA/NETs for mortality in patients with severe burn injury. In a prospective study 32 patients with severe burn injury were included. Blood samples were sequentially obtained on day 1, 3, 5, and 7 after admission. cf-DNA/NETs was directly quantified from plasma by means of rapid fluorescence assay. Time kinetics of cf-DNA/NETs were correlated with clinical data, C-reactive protein (CRP), procalcitonin (PCT), and interleukin (IL)-6. Furthermore sensitivity, specificity, and positive and negative predictive value, as well as receiver operation characteristic (ROC) curves were calculated. Seven patients died within the first month after burn injury. cf-DNA/NETs values from these patients were significantly increased already on day 1 and 3 after admission compared with patients who survived (p < 0.01). In contrast, PCT levels of nonsurvivors were significantly elevated on day 3 and 5 (p < 0.01), while CRP and IL-6 did not show any significant difference between survivors and nonsurvivors. At a cutoff of 255 ng/ml, cf-DNA/NETs had sensitivity of 0.8 and specificity of 0.74. ROC revealed largest areas under the curve (AUC) for cf-DNA/NETs on day 1 (0.851) and 3 (0.883) after admission. For all values between day 1 and 7, AUC was 0.815. cf-DNA/NETs seems to be a rapid, valuable marker for prediction of mortality in burn patients. A larger confirmation trial ought to be carried out.

Outcome prediction in severe burn injury: clinical versus laboratory markers

“…The ROC-curve analysis, which combines sensitivity and specificity of a test, showed a better predictive value, with a larger area under the curve and smaller 95% confidence intervals, than obtained with the cf-DNA/NETs marker: 0.93 (0.84-1.00) vs. 0.85 (0.68-1.00); but as seen in the article of Altrichter, even the 30y old ABSI model appeared to be notably better than the DNA marker with especially a higher specificity and positive predictive value (respectively 92% and 75% for the ABSI model vs. 76% and 46% for the cf-DNA/NETs marker). Therefore, we agree with the authors, that a single parameter such as the cf-DNA/NETs marker should never be used as only predictor of mortality [1].…”

“…These extracellulary DNA structures (produced by neutrophils as defense mechanism trapping and killing pathogens) have previously shown to predict sepsis and mortality in multi-trauma patients [1]. In outcome prediction, mortality is the most objective endpoint, although sepsis and multi-organ failure are also important endpoints [2,3].…”

“…We've read with interest the article of Altrichter et al, in which circulating free-DNA neutrophil extracellular traps (cf-DNA/NETs) were used in the prediction of mortality in a population of 32 patients with severe burn injury [1]. These extracellulary DNA structures (produced by neutrophils as defense mechanism trapping and killing pathogens) have previously shown to predict sepsis and mortality in multi-trauma patients [1].…”

“…These factors are used in the Belgian Outcome in Burn Injury (BOBI) prediction model which repeatedly proved to be easy-to-use and reliable [5][6][7]. In addition, it is definitely less costly since no further (laboratory) analyses are needed as in the study of Altrichter [1]. In the study by Altrichter et al, these cf-DNA/NET markers were compared with the rather outdated ABSI model (1982), after which more than a dozen new severity scoring systems have been developed [5,[8][9][10].…”

Neutrophil extracellular traps in bronchial aspirates: a quantitative analysis

“…However, quantification of NETs in vivo is more difficult than expected because NETs are an extracellular fibrous component, which is difficult to measure precisely by commonly used experimental techniques such as Western blotting, ELISA, PCR, or flow cytometry. Some studies have reported on using the quantity of circulating free DNA to estimate the quantity of NETs in serum [18,19]. However, it is uncertain whether circulating free DNA reflects the amount of NETs directly.…”