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Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is
Ghada M Ezzat1, Soha M Nageb2, Mostafa Abd-Allah Haredi2
1Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Assiut University, Assiut, 71515, Egypt. ghadaezzat@aun.edu.eg.
Background:
Mitochondrial DNA (mtDNA) is a damage-associated molecular pattern molecule that can trigger an immune-inflammatory response during pancreatic necrosis (PN).
Aim:
To evaluate the role of mtDNA in the detection of PN and severe acute pancreatitis (SAP).
Methods:
The present study included 40 AP patients and 30 controls. AP patients were grouped into mild AP (MAP, n = 15), moderately severe AP (MSAP, n = 17), and SAP (n = 8). Also, the SAP + MSAP group, n = 25, was compared to MAP. AP patients were divided into NAP (n = 7) and non-necrotizing AP (n = 33). The mtDNA copy number, IL-6, and STAT3 expression levels were measured using quantitative real-time PCR.
Results:
The mtDNA, IL-6, and STAT3 levels were significantly higher in AP patients than in controls and in the SAP + MSAP than in the MAP. However, the SAP had non-significantly higher levels of mtDNA, STAT3, and IL-6 levels than the MSAP and statistically significant mtDNA, STAT3, and IL-6 when compared to the MAP. mtDNA, IL-6, and STAT3 showed significantly higher levels in NAP compared with non-necrotizing AP. mtDNA was positively correlated with STAT3, IL-6, CRP, APACHE, and CT severity index (CTSI) and negatively correlated with albumin. In the receiver operating curve (ROC), mtDNA was the most significant independent predictor of PN and MAP vs. SAP + MSAP. IL-6 and mtDNA + CRP had higher diagnostic abilities for SIRS and high CTSI.
Conclusions:
mtDNA could enhance the prediction of NAP; however, its diagnostic ability of SAP needs further study.
Insights
Mitochondrial DNA (mtDNA) shows promise in predicting pancreatic necrosis (PN) and distinguishing mild from severe acute pancreatitis (AP). Further research is needed to confirm its diagnostic role in severe acute pancreatitis (SAP).
Area of Science:
- Biochemistry
- Immunology
- Gastroenterology
Background:
- Mitochondrial DNA (mtDNA) acts as a damage-associated molecular pattern molecule.
- mtDNA can initiate immune and inflammatory responses, particularly in pancreatic necrosis (PN).
- Understanding mtDNA's role is crucial for diagnosing and managing acute pancreatitis (AP).
Purpose of the Study:
- To investigate the utility of mitochondrial DNA (mtDNA) in detecting pancreatic necrosis (PN).
- To evaluate mtDNA's role in differentiating between mild and severe forms of acute pancreatitis (AP), including severe acute pancreatitis (SAP).
- To assess the correlation of mtDNA levels with inflammatory markers and disease severity.
Main Methods:
- Quantitative real-time PCR was used to measure mtDNA copy number, IL-6, and STAT3 expression.
- The study included 40 AP patients (classified as mild AP, moderately severe AP, and SAP) and 30 controls.
- Patients were also categorized into non-necrotizing AP and necrotizing AP (NAP) groups.
Main Results:
- Significantly elevated levels of mtDNA, IL-6, and STAT3 were observed in AP patients compared to controls.
- Levels of mtDNA, IL-6, and STAT3 were higher in patients with severe acute pancreatitis (SAP) and necrotizing AP (NAP) compared to mild AP (MAP).
- mtDNA showed a positive correlation with inflammatory markers (CRP, IL-6), disease severity scores (APACHE, CTSI), and STAT3, while negatively correlating with albumin.
Conclusions:
- Mitochondrial DNA (mtDNA) can potentially improve the prediction of necrotizing AP (NAP).
- The diagnostic capability of mtDNA for severe acute pancreatitis (SAP) requires further investigation.
- Combined use of IL-6 and mtDNA with CRP may enhance the diagnosis of systemic inflammatory response syndrome (SIRS) and high CTSI.
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