The Plasma Mitochondrial DNA Is an Independent Predictor for Post-Traumatic Systemic Inflammatory Response Syndrome

et al. (2013) The Plasma Mitochondrial DNA Is an Independent Predictor for Post-Traumatic Systemic Inflammatory Response Syndrome. PLoS ONE 8(8): e72834. doi:10.1371/journal.pone.0072834 The Plasma Mitochondrial DNA Is an Independent Predictor for Post-Traumatic Systemic Inflammatory Response Syndrome Xiaoling Gu 0 Yanwen Yao 0 Guannan Wu 0 Tangfeng Lv 0 Liang Luo 0 Yong Song 0 Cordula M. Stover, University of Leicester, United Kingdom 0 1 Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine , Nanjing , China , 2 Intensive Care Unit, Wu xi Second Affiliated Hospital, Nanjing Medical University , Wu xi , China 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 g/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. - Funding: This present study was supported by the National Natural Scientific Foundation of China Grants (no. 81170064). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Trauma is a global public health problem and is the leading cause of death among people who are below 45 years of age. Twenty percent of these trauma-related deaths occurred several days to weeks after an injury and were mostly due to response syndrome (SIRS), a catastrophic inflammatory response, is a potentially life-threatening trauma-related complication that is observed in up to 30% of trauma patients and is characterized by increases in cellular [2] and noncellular proinflammatory agents [3]. Although the potential of anti-inflammatory agents for modifying inflammatory processes has been clearly established, large-scale clinical studies investigating anti-inflammatory interventions using such modulators have frequently shown little benefit in terms of patient survival [4,5,6]. The failure of these trials has been attributed partially to the current inability to accurately identify high-risk patients at an early stage after injury [7]. Therefore, at present, it continues to be urgent to identify new biomarkers that would aid in the accurate early stratification of populations at high risk for post-traumatic complications, particularly SIRS. In the last ten years, there has been considerable interest in the use of circulating plasma mitochondrial DNA (mtDNA) as a potential marker in various diseases. Plasma mtDNA can be defined as mtDNA fragments that are detectable in circulating plasma. Previous publications have demonstrated that plasma mtDNA could be detected in normal healthy populations, albeit at notably low baseline levels [8]. Simultaneously, elevated levels of plasma mtDNA have been observed in patients with a variety of critical conditions, including malignancy [9,10], acute ischemic stroke [11], severe sepsis [12], corrosive injury [13], and trauma [8]. Lams research group [8] reported that plasma mtDNA increased soon after trauma and was positively correlated with the severity of injury severity. Additionally, a series of studies demonstrated that mtDNA could be recognized by pattern recognition receptors and trigger immune inflammatory responses. Recently, Zhang [14] demonstrated that it is likely that plasma mtDNA that is released into circulation after shock acts in a damageassociated molecular pattern, activating neutrophils and inducing an inflammatory phenotype, ultimately contributing to the initiation of SIRS. Considering the proinflammatory potential of circulating plasma mtDNA, we hypothesised that the circulating plasma mtDNA levels is probably related to the development of post-traumatic inflammation-related complications and has the potential to serve as a predictive indictor for post-traumatic complications, such as SIRS, organ failure and acute lung injury. Although previous studies have demonstrated a significant increase in the level of circulating plasma mtDNA after trauma and that these mtDNA levels are positively associated with the severity of an injury [8], little is known concerning the relationship between plasma mtDNA levels and concrete posttraumatic complications. Therefore, in the present study, we measured the plasma mtDNA levels on admission in both posttraumatic SIRS present patients and post-traumatic SIRS absent patients, and conducted a stepwise logistic regression analysis to investigate the significance of elevated plasma mtDNA levels on admission in terms of its potential to predict post-traumatic complications, particularly SIRS. Patients and Methods Ethics Statement The present study protocol was approved by Jingling Hospitals Institutional Review Committee on Human Research. All patients and healthy adult volunteers provided written informed consent before any study-related procedure was performed. Study population and definition The present study investigating the potential of higher levels of plasma mtDNA in predicting post-traumatic SIRS was conducted in an 11-month period (December 2011 to October 2012). Eighty-six eligible patients at Jingling hospital in Nanjing were recruited. All of these patients were older than 18 and younger than 80 years of age and had been admitted to the emergency ICU department because of an acute tra (...truncated)