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Assessment of circulating cell-free mitochondrial DNA as a damage associated molecular pattern in predicting severity
Bushra1, Safia Begum1, Shaik Iqbal Ahmed1
1Central Laboratory for Stem Cell Research and Translational Medicine, Deccan College of Medical Sciences, Hyderabad, Telangana, 500058, India.
Background:
Sepsis and septic shock are life-threatening conditions with high mortality, presenting challenges in predicting disease severity and outcomes. Cell-free mitochondrial DNA (mtDNA) has emerged as a potential mediator in sepsis pathogenesis, acting as a damage-associated molecular pattern (DAMP) that exacerbates inflammation. The present study aimed to assess cell-free mtDNA levels as predictors of mortality and disease severity, and to determine their correlation with established clinical markers.
Methods:
A prospective study enrolled 150 participants, including healthy controls (n = 50) and patients (n = 100, of which 50 had sepsis and 50 had septic shock). Plasma cell-free mtDNA levels were quantified using RT-qPCR, and Receiver operating characteristic (ROC) curves were used to evaluate the predictive ability of cell-free mtDNA for 28-day mortality. The cell-free mtDNA correlated with clinical markers, including C-reactive protein (CRP), Sequential Organ Failure Assessment (SOFA), Acute Physiology and Chronic Health Evaluation (APACHE II), Procalcitonin (PCT), neutrophil-to-lymphocyte ratio (NLR), and lactate.
Results:
Cell-free mtDNA levels were significantly elevated in sepsis and septic shock patients compared to controls, and higher in septic shock compared to sepsis patients. Non-survivors exhibited significantly higher cell-free mtDNA levels than survivors across both sepsis and septic shock subgroups. Cell-free mtDNA demonstrated a superior predictive value for 28-day mortality, area under the curve (AUC = 0.865) compared to clinical markers (CRP, SOFA, PCT, NLR, and Lactate). Furthermore, cell-free mtDNA levels showed a positive correlation with CRP, followed by SOFA, NLR, and PCT.
Conclusion:
Elevated circulating cell-free mtDNA levels were associated with severity and mortality in sepsis and septic shock, and may act as a valuable molecular tool for predicting disease outcomes. The study's findings warrant further investigation into the potential of cell-free mtDNA as a future component of clinical management strategies in sepsis.
Insights
Cell-free mitochondrial DNA (mtDNA) levels are elevated in sepsis and septic shock, predicting mortality better than clinical markers. Higher mtDNA indicates increased severity and poorer outcomes in these life-threatening conditions.
Area of Science:
- Biochemistry
- Immunology
- Critical Care Medicine
Background:
- Sepsis and septic shock are critical conditions with high mortality rates.
- Cell-free mitochondrial DNA (mtDNA) is implicated in sepsis pathogenesis as a damage-associated molecular pattern (DAMP).
- Predicting sepsis severity and patient outcomes remains a clinical challenge.
Purpose of the Study:
- To evaluate cell-free mtDNA levels as predictors of mortality in sepsis and septic shock.
- To assess cell-free mtDNA's correlation with established clinical severity markers.
- To determine the predictive value of cell-free mtDNA for disease outcomes.
Main Methods:
- Prospective study of 150 participants (50 healthy controls, 50 sepsis, 50 septic shock).
- Quantification of plasma cell-free mtDNA using RT-qPCR.
- Receiver operating characteristic (ROC) curve analysis for mortality prediction and correlation with CRP, SOFA, APACHE II, PCT, NLR, and lactate.
Main Results:
- Cell-free mtDNA levels were significantly higher in sepsis and septic shock patients versus controls.
- Non-survivors had markedly elevated cell-free mtDNA levels compared to survivors.
- Cell-free mtDNA showed superior predictive value for 28-day mortality (AUC=0.865) over clinical markers and correlated positively with CRP, SOFA, NLR, and PCT.
Conclusions:
- Elevated cell-free mtDNA is associated with increased severity and mortality in sepsis and septic shock.
- Cell-free mtDNA serves as a potential molecular biomarker for predicting sepsis outcomes.
- Further research is warranted to integrate cell-free mtDNA into clinical sepsis management.
