Diagnostic value of mitochondrial DNA and peripheral blood mononuclear cell respirometry for burn-related sepsis

BACKGROUND: Sepsis is the leading cause of mortality among burn patients that survive acute resuscitation. Clinical criteria have poor diagnostic value for burn induced sepsis, making it difficult to diagnose. Protein biomarkers (e.g., procalcitonin) have been examined with limited success. We aimed to explore other biomarkers related to mitochondria (mitochondrial DNA (mtDNA) and mitochondrial function of peripheral blood mononuclear cells (PBMCs) for sepsis diagnosis in burn patients.

METHODS: We conducted a follow-up analysis of a single center, prospective observational study of subjects (n = 10 healthy volunteers, n = 24 burn patients) to examine the diagnostic value of mtDNA and PBMC respirometry. Patients were enrolled regardless of sepsis status and followed longitudinally. Patient samples were classified as septic or not based on empiric clinical criteria. Isolated PBMCs were loaded into a high-resolution respirometer, and circulating mtDNA was measured with a PCR-based assay. Sequential Organ Failure Assessment (SOFA) criteria were also compared.

RESULTS: SOFA criteria comparing septic versus before/non-septic patients revealed significantly higher heart rate (p = 0.012) and lower mean arterial pressure (p = 0.039) in burn sepsis. MtDNA was significantly elevated in septic burn patients compared to healthy volunteers (p < 0.0001) and non-septic patients (p < 0.0001), with no significant difference between healthy volunteers and non-septic burn patients (p = 0.187). The area under the ROC curve (AUC) for mtDNA was 0.685 (95% CI = 0.50-0.86). For PBMC respirometry, burn patients exhibited increased routine and maximal respiration (MR) potential compared to healthy volunteers. However, no difference was found between non-septic and septic patient samples. A sub-analysis revealed a significant mortality difference in PBMC respirometry after sepsis diagnosis, wherein survivors had higher routine respiration (p = 0.003) and MR (p = 0.011) compared to non-survivors.

CONCLUSION: Our findings reveal that mtDNA may have diagnostic value for burn sepsis, while PBMC respirometry is non-specifically elevated, but may have value in mortality prognosis. A larger, multi-site study is warranted for further validity of the diagnostic value of mtDNA and PBMC respirometry as biomarkers for prognosis of sepsis and outcomes in burn patients.