From the Abdominal Center, Department of Abdominal Surgery.
Bacteriology and Immunology, Helsinki University Hospital and University of Helsinki, Helsinki, Finland.
Pancreas. 2021;50(5):710-718. doi: 10.1097/MPA.0000000000001832.
Clinical practice lacks biomarkers to predict the severity of acute pancreatitis (AP). We studied if intracellular signaling of circulating leukocytes could predict persistent organ dysfunction (OD) and secondary infections in AP.
A venous blood sample was taken from 174 patients with AP 72 hours or less from onset of symptoms and 31 healthy controls. Phosphorylation levels (p) of appropriately stimulated signal transducer and activator of transcription 1 (STAT1), STAT6, nuclear factor-κB (NF-κB), Akt, and nonstimulated STAT3 in monocytes, neutrophils, and lymphocytes was measured using phosphospecific flow cytometry.
The patients showed higher pSTAT3 and lower pSTAT1, pSTAT6, pNF-κB, and pAkt than healthy controls. pSTAT3 in all leukocyte subtypes studied increased, and pSTAT1 in monocytes and T cells decreased in an AP severity-wise manner. In patients without OD at sampling, high pSTAT3 in monocytes and T lymphocytes were associated with development of persistent OD. In patients with OD, low interleukin-4-stimulated pSTAT6 in monocytes and neutrophils and Escherichia coli-stimulated pNF-κB in neutrophils predicted OD persistence. High pSTAT3 in monocytes, CD8+ T cells, and neutrophils; low pSTAT1 in monocytes and T cells; and low pNF-κB in lymphocytes predicted secondary infections.
Leukocyte STAT3, STAT1, STAT6, and NF-κΒ phosphorylations are potential predictors of AP severity.
临床实践缺乏预测急性胰腺炎（AP）严重程度的生物标志物。我们研究了循环白细胞的细胞内信号是否可以预测 AP 中的持续性器官功能障碍（OD）和继发感染。
从发病后 72 小时内的 174 例 AP 患者和 31 名健康对照者采集静脉血样本。使用磷酸化特异性流式细胞术测量单核细胞、中性粒细胞和淋巴细胞中适当刺激的信号转导和转录激活因子 1（STAT1）、STAT6、核因子-κB（NF-κB）、Akt 和非刺激 STAT3 的磷酸化水平（p）。
与健康对照组相比，患者表现出更高的 pSTAT3 和更低的 pSTAT1、pSTAT6、pNF-κB 和 pAkt。研究的所有白细胞亚型中的 pSTAT3 增加，而单核细胞和 T 细胞中的 pSTAT1 则以 AP 严重程度的方式减少。在采样时无 OD 的患者中，单核细胞和 T 淋巴细胞中的高 pSTAT3 与持续 OD 的发展相关。在有 OD 的患者中，单核细胞和中性粒细胞中白细胞介素-4 刺激的低 pSTAT6 和中性粒细胞中大肠杆菌刺激的低 pNF-κB 预测 OD 持续存在。单核细胞、CD8+T 细胞和中性粒细胞中的高 pSTAT3；单核细胞和 T 细胞中的低 pSTAT1；以及淋巴细胞中的低 pNF-κB 预测继发感染。
白细胞 STAT3、STAT1、STAT6 和 NF-κB 磷酸化可能是 AP 严重程度的预测指标。
