Ren Zhibo, Ji Jinke, Lou Caili, Gao Yuxin, Feng Xueyan, Ye Qiang, Jia Wei, Zhang Xu, Niu Ningkui
Department of Orthopedics General Hospital of Ningxia Medical University Yinchuan China.
School of Clinical Medicine Ningxia Medical University Yinchuan China.
JOR Spine. 2024 Apr 10;7(2):e1331. doi: 10.1002/jsp2.1331. eCollection 2024 Jun.
The objective of this study is to evaluate the value of S100-A8 protein as a diagnostic marker for spinal tuberculosis and to explore its role in the potential pathogenesis of spinal tuberculosis (STB).
The peripheral blood of 100 spinal tuberculosis patients admitted to the General Hospital of Ningxia Medical University from September 2018 to June 2021 were collected as the observation group, and the peripheral blood of 30 healthy medical examiners were collected as the control group. Three samples from the observation group and three samples from the control group were selected for proteomics detection and screening of differential proteins. Kyoto Encyclopedia of Genes (KEGG) was used to enrich and analyze related signaling pathways to confirm the target protein. The serum expression levels of the target proteins were determined and compared between the two groups using enzyme-linked immunosorbent assay (ELISA). Statistical methods were used to evaluate the value of target protein as a diagnostic marker for STB. A macrophage model of infection was constructed and S100-A8 small interfering RNA was used to investigate the molecular mechanism of the target protein.
S100-A8 protein has the value of diagnosing spinal tuberculosis (AUC = 0.931, < 0.001), and the expression level in the peripheral blood of the observation group (59.04 ± 19.37 ng/mL) was significantly higher than that of the control group (43.16 ± 10.07 ng/mL) ( < 0.05). S100-A8 protein expression showed a significant positive correlation with both CRP and ESR values ( < 0.01). Its AUCs for combined bacteriological detection, T-SPOT results, diagnostic imaging, antacid staining results, and pathological results were 0.705 ( < 0.05), 0.754 ( < 0.01), 0.716 ( < 0.01), 0.656 ( < 0.05), and 0.681 ( < 0.01), respectively. Lack of S100-A8 leads to a significant decrease in the expression levels of TLR4 and IL-17A in infected macrophages.
S100-A8 protein is differentially expressed in the peripheral blood of patients with spinal tuberculosis and healthy individuals and may be a novel candidate biomarker for the diagnosis of spinal tuberculosis. The feedback loop on the S100-A8-TLR4-IL-17A axis may play an important role in the inflammatory mechanism of spinal tuberculosis.
本研究旨在评估S100 - A8蛋白作为脊柱结核诊断标志物的价值,并探讨其在脊柱结核潜在发病机制中的作用。
收集2018年9月至2021年6月在宁夏医科大学总医院收治的100例脊柱结核患者的外周血作为观察组,收集30例健康体检者的外周血作为对照组。从观察组和对照组中各选取3份样本进行蛋白质组学检测及差异蛋白筛选。采用京都基因与基因组百科全书(KEGG)对相关信号通路进行富集分析以确定目标蛋白。采用酶联免疫吸附测定(ELISA)法测定并比较两组目标蛋白的血清表达水平。运用统计学方法评估目标蛋白作为脊柱结核诊断标志物的价值。构建感染巨噬细胞模型,使用S100 - A8小干扰RNA研究目标蛋白的分子机制。
S100 - A8蛋白具有诊断脊柱结核的价值(AUC = 0.931,P < 0.001),观察组外周血中该蛋白表达水平(59.04 ± 19.37 ng/mL)显著高于对照组(43.16 ± 10.07 ng/mL)(P < 0.05)。S100 - A8蛋白表达与CRP和ESR值均呈显著正相关(P < 0.01)。其联合细菌学检测、T - SPOT结果、诊断性影像学、抗酸染色结果及病理结果的AUC分别为0.705(P < 0.05)、0.754(P < 0.01)、0.716(P < 0.01)、0.656(P < 0.05)和0.681(P < 0.01)。S100 - A8蛋白缺失导致感染巨噬细胞中TLR4和IL - 17A表达水平显著降低。
S100 - A8蛋白在脊柱结核患者和健康个体外周血中存在差异表达,可能是诊断脊柱结核的新型候选生物标志物。S100 - A8 - TLR4 - IL - 17A轴上的反馈环可能在脊柱结核的炎症机制中起重要作用。