白细胞中高迁移率族蛋白 B1 的表达作为[Tc]Tc-HMPAO 标记程序诱导的细胞损伤的生物标志物：一项质量控制研究。
HMGB1 expression in leukocytes as a biomarker of cellular damage induced by [Tc]Tc-HMPAO-labelling procedure: A quality control study.
机构信息
Nuclear Medicine Unit, Department of Radiology, Oncology and Human Pathology, "Sapienza" University of Rome, Italy; Molecular Medicine PhD Program, Department of Molecular Medicine, "Sapienza" University of Rome, Italy.
Department of Experimental Medicine, "Sapienza" University of Rome, Italy.
出版信息
Nucl Med Biol. 2021 May-Jun;96-97:94-100. doi: 10.1016/j.nucmedbio.2021.03.008. Epub 2021 Apr 9.
PURPOSE
Autologous White Blood Cells (WBC) scintigraphy is based on a multi-step sequence of cell separation and radiolabelling. Besides in vivo imaging quality control, no molecular tool is available to evaluate WBC damage secondary to cell manipulation. High Mobility Group Box 1 (HMGB1) is a protein of the alarmins family, secreted by innate immune cells and released from the nucleus of damaged cells following different types of injury. Aim of this study was to evaluate HMGB1 levels in WBC cytosolic extracts (CE) before and after [Tc]Tc-HMPAO labelling procedure, as a biomarker of induced WBC damage.
PROCEDURES
Patients with suspect of prosthetic joint infection were prospectively enrolled. HMGB1 levels were evaluated by immunoblotting analysis in plasma (t), and in WBC-CE before (t) and after (t) [Tc]Tc-HMPAO labelling. Blood samples from healthy subjects were evaluated under the same procedure.
RESULTS
Twenty consecutive patients referred for WBC scintigraphy and ten controls were enrolled. HMGB1 levels were significantly upregulated both in plasma (t) and in circulating WBC-CE (t) from patients compared to controls (p < 0.0001). Otherwise, WBC-CE from [Tc]Tc-HMPAO-labelled leukocyte concentrate (t) did not show significant changes in HMGB1 levels compared to the cold leukocyte sample (t).
CONCLUSIONS
The evaluation of HMGB1 levels in WBC-CE from each subject after radiolabelling with [Tc]Tc-HMPAO did not show significant changes compared to the cold cellular sample. These results further prove the reliability of [Tc]Tc-HMPAO leukocyte radiolabelling procedure in terms of cell viability and suggest that the monitoring of this alarmin may represent a specific tool to evaluate a secondary damage of WBC induced by radiolabelling procedure. In addition, significant upregulation of HMGB1 levels was found in WBC-CE and in plasma from patients with suspect of PJI - compared to healthy donors - reasonably related to their underlying inflammatory/infective condition.
目的
自体白细胞（WBC）闪烁照相术基于细胞分离和放射性标记的多步序列。除了体内成像质量控制外，没有分子工具可用于评估细胞操作引起的 WBC 损伤。高迁移率族蛋白 B1（HMGB1）是警报素家族的一种蛋白质，由先天免疫细胞分泌，并在不同类型的损伤后从受损细胞的核中释放。本研究旨在评估[Tc]Tc-HMPAO 标记程序前后 WBC 胞质提取物（CE）中的 HMGB1 水平，作为诱导的 WBC 损伤的生物标志物。
程序
前瞻性纳入怀疑人工关节感染的患者。通过免疫印迹分析评估血浆（t）和[Tc]Tc-HMPAO 标记前（t）和后（t）的 WBC-CE 中的 HMGB1 水平。在相同的程序下评估健康受试者的血液样本。
结果
连续纳入 20 例接受 WBC 闪烁照相术的患者和 10 例对照者。与对照组相比，HMGB1 水平在患者的血浆（t）和循环 WBC-CE（t）中均显著上调（p < 0.0001）。然而，与冷白细胞样本（t）相比，[Tc]Tc-HMPAO 标记白细胞浓缩物（t）中的 WBC-CE 中 HMGB1 水平没有显著变化。
结论
与冷细胞样本相比，用[Tc]Tc-HMPAO 对每个受试者的 WBC-CE 进行放射性标记后，HMGB1 水平的评估没有显著变化。这些结果进一步证明了[Tc]Tc-HMPAO 白细胞放射性标记程序在细胞活力方面的可靠性，并表明监测这种警报素可能是评估放射性标记程序引起的 WBC 继发性损伤的特定工具。此外，在怀疑 PJI 的患者的 WBC-CE 和血浆中发现 HMGB1 水平显著上调-与健康供体相比-这与他们潜在的炎症/感染状况合理相关。
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