The plasma mitochondrial DNA is an independent predictor for post-traumatic systemic inflammatory response syndrome

Abstract

Background and purpose: Mitochondrial DNA (mtDNA), a newly identified damage-associated molecular pattern, has been observed in trauma patients, however, little is known concerning the relationship between plasma mtDNA levels and concrete post-traumatic complications, particularly systemic inflammatory response syndrome (SIRS). The aim of this study is to determine whether plasma mtDNA levels are associated with injury severity and cloud predict post-traumatic SIRS in patients with acute traumatic injury.

Patients and methods: Eighty-six consecutive patients with acute traumatic injury were prospectively enrolled in this study. The plasma mtDNA concentration was measured by a real-time, quantitative PCR assay for the human ND2 gene. The study population's clinical and laboratory data were analyzed.

Results: The median plasma mtDNA was higher in trauma patients than in healthy controls (865.196 (251.042-2565.40)pg/ml vs 64.2147 (43.9049-80.6371)pg/ml, P<0.001) and was independently correlated with the ISS score (r=0.287, P<0.001). The plasma mtDNA concentration was also significantly higher in patients who developed post-traumatic SIRS than in patients who did not (1774.03 (564.870-10901.3)pg/ml vs 500.496 (145.415-1285.60)pg/ml, P<0.001). Multiple logistic regression analysis revealed that the plasma mtDNA was an independent predictors for post-traumatic SIRS (OR, 1.183 (95%CI, 1.015-1.379), P=0.032). Further ROC analysis demonstrated that a high plasma mtDNA level predicted post-traumatic SIRS with a sensitivity of 67% and a specificity of 76%, with a cut-off value of 1.3185 µg/ml being established, and the area under the ROC curves (AUC) was 0.725 (95% CI 0.613-0.837).

Conclusions: Plasma mtDNA was an independent indictor with moderate discriminative power to predict the risk of post-traumatic SIRS.

Figure 1. Box plots of the plasma mitochondrial DNA concentration between the trauma patients and healthy controls.

Plasma mtDNA concentrations presented as median values (line across the boxes), IQR (limits of the boxes), and 5^th to 95^th percentiles (whiskers). The plasma mtDNA concentration in the traumatic patients was significantly higher than for the healthy controls (P<0.001).

Figure 2. Box plots of the plasma mitochondrial DNA concentration in patients stratified by post-traumatic systemic inflammatory response syndrome present or absent.

Plasma mtDNA concentrations presented as median values (line across the boxes), IQR (limits of the boxes), and 5^th to 95^th percentiles (whiskers). The plasma mtDNA concentration in patients who developed post-traumatic SIRS was significantly higher than for those who did not (P<0.001).

Figure 3. Box plots of plasma mitochondrial DNA concentration in trauma patients stratified by the severity of injury.

Plasma mtDNA concentrations presented as median values (line across the boxes), IQR (limits of the boxes), and 5^th to 95^th percentiles (whiskers). Plasma mtDNA concentrations in traumatic patients with ISS ≧ 16 were significantly higher than in patients with ISS < 16 (P<0.001).

Figure 4. Receiver operator characteristics curves for plasma mitochondrial DNA levels, C-reactive protein concentrations and white blood cell count in predicting post-traumatic SIRS.

The AUCs for plasma mitochondrial DNA, C-reactive protein and white blood cell count was 0.725(95%CI 0.613-0.837), 0.751(95%CI 0.646-0.855) and 0.853(95%CI 0.775-0.932), respectively.