Department of Medicine, University of Arizona Health Sciences, Tucson, AZ, USA.
University of Ulsan College of Medicine, Asan Medical Center, Seoul, Korea.
BMC Anesthesiol. 2022 Jun 15;22(1):182. doi: 10.1186/s12871-022-01718-1.
Nicotinamide phosphoribosyltransferase (NAMPT) exhibits dual functionality - as an intracellular enzyme regulating nicotinamide adenine dinucleotide metabolism and as an extracellular secreted protein (eNAMPT) to function as a cytokine regulator of innate immunity via binding to Toll-Like receptor 4 and NF-κB activation. In limited preclinical and clinical studies, eNAMPT was implicated in the pathobiology of acute respiratory distress syndrome (ARDS) suggesting that eNAMPT could potentially serve as a diagnostic and prognostic biomarker. We investigated the feasibility of circulating eNAMPT levels to serve as a biomarker in an expanded cohort of patients with ARDS and ARDS-predisposing conditions that included acute pancreatitis, sepsis, and trauma with comparisons to controls.
A total of 671 patients and 179 healthy controls were included in two independent cohorts. Plasma and serum eNAMPT levels were quantified using one of two complementary Enzyme-linked Immunosorbent Assays. After log base 2 variance stabilizing transformation of plasma/serum eNAMPT measurements, differences between healthy controls and each disease cohort were compared using linear regression or a generalized estimating equation (GEE) model where applicable. Complementary analyses included sensitivity, specificity, positive predictive values, negative predictive values, and the area under the receiver operating curve.
Compared to controls, circulating eNAMPT levels were significantly elevated in subjects with acute pancreatitis, sepsis, trauma, and ARDS (all p < 0.01). In the acute pancreatitis cohort, circulating eNAMPT levels positively correlated with disease severity (p < 0.01).
Circulating eNAMPT levels are novel biomarker in the critically ill with acute pancreatitis, sepsis, trauma, and/or ARDS with the potential to reflect disease severity.
烟酰胺磷酸核糖基转移酶（NAMPT）具有双重功能 - 作为一种调节烟酰胺腺嘌呤二核苷酸代谢的细胞内酶，以及一种作为细胞外分泌蛋白（eNAMPT）的细胞因子调节剂，通过与 Toll 样受体 4 结合和 NF-κB 激活来调节先天免疫。在有限的临床前和临床研究中，eNAMPT 与急性呼吸窘迫综合征（ARDS）的病理生理学有关，这表明 eNAMPT 可能作为一种诊断和预后生物标志物。我们研究了循环 eNAMPT 水平作为 ARDS 患者和 ARDS 易感患者扩展队列中的生物标志物的可行性，这些患者包括急性胰腺炎、败血症和创伤，并与对照组进行了比较。
共有 671 名患者和 179 名健康对照者纳入了两个独立的队列。使用两种互补的酶联免疫吸附测定法之一来定量血浆和血清 eNAMPT 水平。对血浆/血清 eNAMPT 测量值进行对数 base 2 方差稳定化转换后，使用线性回归或广义估计方程（GEE）模型比较健康对照组和每个疾病队列之间的差异，在适用的情况下。补充分析包括敏感性、特异性、阳性预测值、阴性预测值和接收器操作曲线下的面积。
与对照组相比，急性胰腺炎、败血症、创伤和 ARDS 患者的循环 eNAMPT 水平明显升高（均 p<0.01）。在急性胰腺炎队列中，循环 eNAMPT 水平与疾病严重程度呈正相关（p<0.01）。
循环 eNAMPT 水平是急性胰腺炎、败血症、创伤和/或 ARDS 重症患者的新型生物标志物，具有反映疾病严重程度的潜力。
