Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Division of Gastroenterology, Hepatology and Nutrition, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
PLoS One. 2022 Feb 14;17(2):e0261708. doi: 10.1371/journal.pone.0261708. eCollection 2022.
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.
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.
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).
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.
成人和儿科患者的急性胰腺炎 (AP) 的发病率正在增加。识别有进展为重症急性胰腺炎 (SAP) 风险的患者至关重要，因为这会导致死亡率和医疗系统成本增加。基质金属蛋白酶 (MMPs) 是内肽酶，可降解细胞外基质蛋白并增加促炎细胞因子的活性。金属蛋白酶组织抑制剂 (TIMPs) 调节 MMP 活性。先前对 MMPs 和 TIMPs 的有限研究发现，其中一些与 SAP 的发展有关。本研究旨在进一步研究 MMPs 和 TIMPs 在检测有发展为中度严重 AP 或 SAP 风险的儿科患者中的作用。
前瞻性收集了 2015 年 11 月至 2019 年 10 月期间患有 AP 的<21 岁患者和健康对照者的血浆样本。使用基于珠的多重分析检测 12 种 MMPs 和 TIMPs 的水平。
从 7 例发生 SAP、7 例中重度 AP、45 例轻度 AP 和 44 例健康对照者中采集了样本。SAP 患者的 MMP-9（p=0.04）和 TIMP-1（p=0.01）水平显著升高。使用 MMP-9 和 TIMP-1 的多变量逻辑回归模型预测 SAP（AUROC 0.87，95%CI 0.76-0.98）。
我们已经证明，在发病期间发生 SAP 的儿科患者的 AP 表现中，MMP9 和 TIMP1 水平升高。需要进一步研究以验证 MMPs 和 TIMPs 作为预测儿科胰腺炎 SAP 发展的工具的使用。
