Mitochondrial DNA Copy Number, a Damage-Associated Molecular Pattern Molecule, Can Predict Pancreatic Necrosis and Is Correlated with the Severity of Acute Pancreatitis

Dig Dis Sci. 2023 Nov;68(11):4175-4185. doi: 10.1007/s10620-023-08049-2. Epub 2023 Sep 7.

Abstract

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.

Keywords: Acute necrotizing pancreatitis; Detecting ability; IL-6; STAT3; Severe acute pancreatitis; mtDNA.