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Matrix metalloproteinases and their inhibitors in pediatric severe acute pancreatitis
David S Vitale1,2, Patrick Lahni1,3, Lindsey Hornung4
1Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Insights
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) may help identify children at risk for severe acute pancreatitis (SAP). Elevated MMP-9 and TIMP-1 levels at presentation indicate higher risk for developing SAP.
Area of Science:
- Biochemistry
- Pediatric Gastroenterology
- Biomarker Discovery
Background:
- Acute pancreatitis (AP) incidence is rising in children and adults.
- Identifying patients at high risk for severe acute pancreatitis (SAP) is critical due to mortality and cost.
- Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are implicated in AP pathogenesis.
Purpose of the Study:
- To investigate the role of MMPs and TIMPs in predicting SAP risk in pediatric patients.
- To identify specific MMPs and TIMPs associated with the progression of AP to SAP.
Main Methods:
- Prospective collection of plasma samples from pediatric AP patients and healthy controls.
- Utilized bead-based multiplex assays to measure levels of 12 MMPs and TIMPs.
- Analyzed biomarker levels in patients with mild AP, moderately severe AP, and SAP.
Main Results:
- MMP-9 and TIMP-1 levels were significantly elevated in pediatric patients who developed SAP.
- A multivariable logistic regression model incorporating MMP-9 and TIMP-1 accurately predicted SAP (AUROC 0.87).
Conclusions:
- Elevated MMP-9 and TIMP-1 levels at AP presentation are associated with SAP development in children.
- MMPs and TIMPs show potential as predictive biomarkers for SAP in pediatric pancreatitis.
- Further validation studies are required to confirm their clinical utility.
Background:
Acute pancreatitis (AP) is increasing in incidence in adult and pediatric patients. Identification of patients at high risk for progression to severe acute pancreatitis (SAP) is crucial, as it can lead to increased mortality and health system cost. Matrix metalloproteinases (MMPs) are endopeptidases which degrade extracellular matrix proteins and increase activity of pro-inflammatory cytokines. Tissue inhibitors of metalloproteinases (TIMPs) regulate MMP activity. Prior limited studies of MMPs and TIMPs have found some to be associated with development of SAP. The aim of this study was to further investigate the role of MMPs and TIMPs in detecting pediatric patients at risk for developing moderately severe AP or SAP.
Methods:
Plasma samples were prospectively collected for patients <21 years of age presenting with AP between November 2015 and October 2019, along with healthy controls. Bead-based multiplex assays were utilized to test levels of 12 MMPs and TIMPs.
Results:
Samples were collected from 7 subjects who developed SAP, 7 with moderately severe AP, 45 with mild AP and 44 healthy controls. MMP-9 (p = 0.04) and TIMP-1 (p = 0.01) levels were significantly higher in SAP patients. A multivariable logistic regression model using MMP-9 and TIMP-1 predicted SAP (AUROC 0.87, 95% CI 0.76-0.98).
Conclusion:
We have demonstrated that MMP9 and TIMP1 levels are increased at AP presentation in pediatric patients who developed SAP during the course of illness. Further studies are needed to validate the use of MMPs and TIMPs as predictive tools for development of SAP in pediatric pancreatitis.
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