Department of Pediatrics, School of Medicine, Institute of Medical, Pharmaceutical, and Health Sciences, Kanazawa University, Kanazawa, Japan.
Department of Child Health and Development, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan.
Ren Fail. 2021 Dec;43(1):382-387. doi: 10.1080/0886022X.2021.1885445.
Insulin-like growth factor-binding protein (IGFBP) 2 plays an important role in the regulation of cell adhesion, migration, growth, and apoptosis. This study aimed to investigate the clinical significance of serum IGFBP2 as a biomarker for disease activity and severity in hemolytic uremic syndrome (HUS) induced by enterohemorrhagic (EHEC).
IGFBP2 production by human renal glomerular endothelial cells (RGECs) after exposure to Shiga toxin 2 (Stx-2) was investigated . Serum IGFBP2 levels in blood samples obtained from 22 patients with HUS and 10 healthy controls (HCs) were quantified using an enzyme-linked immunosorbent assay. The results were compared to the clinical features of HUS and serum tau and cytokine levels.
Stx-2 induced the production of IGFBP2 in RGECs in a dose-dependent manner. Serum IGFBP2 levels were significantly higher in patients with HUS than in HCs and correlated with disease severity. Additionally, serum IGFBP2 levels were significantly higher in patients with encephalopathy than in those without encephalopathy. A serum IGFBP2 level above 3585 pg/mL was associated with a high risk of encephalopathy. Furthermore, serum IGFBP2 levels significantly correlated with serum levels of tau and inflammatory cytokines associated with the development of HUS.
Correlation of serum IGFBP2 level with disease activity in patients with HUS suggests that IGFBP2 may be considered as a possible indicator for disease activity and severity in HUS. Larger studies and additional experiments using various cells in central nervous system should elucidate the true value of IGFBP2 as a clinical diagnostic marker.
IGFBP: insulin-like growth factor-binding protein; HUS: hemolytic uremic syndrome; EHEC: enterohemorrhagic Escherichia coli; RGECs: renal glomerular endothelial cells; STx-2: Shiga toxin 2; HCs: healthy controls; LPS: lipopolysaccharide; ROC: receiver operating characteristic; sTNFR: soluble tumor necrosis factor receptor.
胰岛素样生长因子结合蛋白 2（IGFBP2）在调节细胞黏附、迁移、生长和凋亡方面发挥着重要作用。本研究旨在探讨血清 IGFBP2 作为肠出血性大肠杆菌（EHEC）诱导的溶血性尿毒症综合征（HUS）疾病活动和严重程度的生物标志物的临床意义。
研究了人肾小球内皮细胞（RGECs）在暴露于志贺毒素 2（Stx-2）后产生 IGFBP2 的情况。采用酶联免疫吸附试验（ELISA）定量检测 22 例 HUS 患者和 10 例健康对照（HC）的血液样本中 IGFBP2 水平。并将结果与 HUS 的临床特征、血清 tau 和细胞因子水平进行比较。
Stx-2 以剂量依赖的方式诱导 RGECs 产生 IGFBP2。HUS 患者的血清 IGFBP2 水平明显高于 HC，且与疾病严重程度相关。此外，有脑病的患者血清 IGFBP2 水平明显高于无脑病的患者。血清 IGFBP2 水平高于 3585pg/ml 与脑病风险增加相关。此外，血清 IGFBP2 水平与与 HUS 发生相关的 tau 和炎症细胞因子的血清水平显著相关。
HUS 患者血清 IGFBP2 水平与疾病活动的相关性提示 IGFBP2 可作为 HUS 疾病活动和严重程度的一个可能指标。更大规模的研究和使用中枢神经系统中各种细胞的额外实验，应阐明 IGFBP2 作为临床诊断标志物的真正价值。
IGFBP：胰岛素样生长因子结合蛋白；HUS：溶血性尿毒症综合征；EHEC：肠出血性大肠杆菌；RGECs：肾小球内皮细胞；STx-2：志贺毒素 2；HCs：健康对照；LPS：脂多糖；ROC：受试者工作特征；sTNFR：可溶性肿瘤坏死因子受体。
