The Value Of Plasma Mitochondrial DNA Levels To The Severity And Prognosis In Children With Sepsis

Background Sepsis is systemic inflammatory response syndrome caused by infection. The mortality and incidence rate of sepsis are extremely high., and it easily develop to septic shock and multiple organ dysfunction, has become a thorny problem currently facing in PICU. Early diagnosis and evaluation of sepsis is essential for reducing the mortality rate. However, Numerous biomarkers for predicting morbidity and mortality in the critical care setting have been evaluated, but none have been proven entirely useful., such as C-reactive protein(C-reactive protein, CRP), procalcitonin(procalcitonin, PCT) and scoring systems. Plasma free DNA can be defined as DNA fragments that are detectable in extracellular fluid and are of two types: mitochondrial DNA(Mitochondrial DNA, mt-DNA) and nuclear DNA(Nuclear DNA, n-DNA), Which can be released into the blood from apoptotic and necrotic cells. However mt-DNA had received broader concerns for its characteristic of Short length, simple structure and high copy number. There are studies have shown that plasma mt-DNA elevated abnormally in adult sepsis, and it have a certain value for judgment of sepsis. What’s more, it predict mortality with higher specificity and sensitivity, better than PCT, CRP and other indicators, but there are few studies in this filed for children.Objective To investigate the value of plasma mt-DNA levers to determine the severity and mortality of children sepsis, and explore new sepsis biomarkers for early diagnosis of organ dysfunction.Methods 123 cases of children with sepsis who hospitalized in Hunan Children’s Hospital PICU from July 2013 to December 2014, They are divided into general group(n=70) and severe sepsis group(53 cases) according to the severity of disease. We randomly select another 30 children with non-sepsis infection, 30 healthy children as control group. We collect plasma when children were admitted. plasma mt-DNA levers was detected using real-time PCR technology. At the same time we made PCIS, SOFA score after admission, and use Epidata records clinical laboratory data, such as CRP, PCT, blood lactate and other testing data.Results(1)Comparasion between Sepsis group and control groupThe levels of plasma mt-DNA in sepsis group is increased compared with the non-sepsis infection group and healthy control group.(2) plasma mt-DNA and severity of sepsis① plasma mt-DNA, PCT, lactic acid and CRP in sever sepsis group were significantly higher than general sepsis group(P <0.001), but the difference of CRP was not statistically significance(P> 0.05).② according to the different level of PCIS score, sepsis cases were divided into more than 90 points, 81 to 90 points, 71 to 80 points, and 70 points or less four points, the result show: with the PCIS score lower plasma mt-DNA, PCT, Lac gradually rises(P <0.01), but CRP did not decrease with PCIS increased, the difference was not statistically significant(P> 0.05).③ All sepsis cases were divided into three group according to the number of organ dysfunction on admission: without organ dysfunction, 1 to 2 organ dysfunction group, multiple organ dysfunction group(≥3 months), We found that more the number of organ dysfunction, the higher level of plasma mt-DNA, CRP, PCT, lac were, and mt-DNA, CRP, PCT, Lac had statistics significance difference(P <0.001), but CRP had no significant difference(P> 0.05).④ Plasma mt-DNA in the Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lactate dehydrogenase, creatine kinase, myoglobin, creatine kinase MB, troponin and other organ function index increased group was higher than normal group(P <0.01).(3) Plasma mt-DNA and prognosis① Plasma mt-DNA, CRP, PCT, Lac in non-survival group were higher than survival group, and plasma mt-DNA, PCT, Lac difference was statistically significant(P <0.001), but CRP difference was no significant(P> 0.05).② Plasma mt-DNA levels, CRP, PCT, blood lactate of area(AUC) under ROC curves were: 0.745, 0.629, 0.776, 0.864, and plasma mt-DNA PCT, blood lactate difference was statistically significant(P <0.001), but CRP difference was no significant(P> 0.05). mt-DNA≥890.43 pg / ml, PCT≥6.88 ug / L, blood lactate acid≥2.15 mmol / L act as cut-off point to determine the prognosis of death, the results show the sensitivity and specificity of mt-DNA,PCT, blood lactic acid were 88.5%、53.6%; 73.1%、71.3%; 88.5%、 77.4%。(4)Correlation between plasma mt-DNA and PCT, Lac, SOFA score, PCISThere were negatively correlated between plasma Mt-DNA and PCIS(P <0.001, and were positively correlated between plasma Mt-DNA and PCT, Lac, SOFA scores(P <0.01), plasma mt-DNA was not associated with CRP(P> 0.05).Conclusion(1) Plasma mitochondrial DNA levels increased abnormally in children with sepsis, and it can help to determine the severity of sepsis, may be can be used as a biomarker for early diagnosis and disease assessment.(2) Plasma mitochondrial DNA levels were significantly elevated in children with sepsis, which Indicates poor prognosis, and it help to determine the prognosis of sepsis with good value, may be can be used as a biomarker for prognosis of children with sepsis.