Chen Ximeng, Wang Jianan, Wang Jinyang, Ye Jingyun, Di Ping, Dong Chang, Lei Hong, Wang Chengbin
Medical School of Chinese PLA, No.28 Fuxing Road, Haidian District, Beijing, China; Department of Clinical Laboratory Medicine, The First Medical Center, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, China.
Department of Clinical Laboratory Medicine, The First Medical Center, Chinese PLA General Hospital, No.28 Fuxing Road, Haidian District, Beijing, China.
Clin Chim Acta. 2023 Jul 1;547:117447. doi: 10.1016/j.cca.2023.117447. Epub 2023 Jun 21.
Osteoarticular tuberculosis is one of the extrapulmonary tuberculosis (EPTB) diseases, which is mainly caused by infection of Mycobacterium tuberculosis (MTB) in bone and joints. The limitation of current clinical test methods is leading to a high misdiagnosis rate and affecting the treatment and prognosis. This study aims to search serum biomarkers that can assist in the diagnosis of osteoarticular tuberculosis.
Proteomics can serve as an important method in the discovery of disease biomarkers. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to analyze proteins in 90 serum samples, which were collected from June 2020 to December 2021, then evaluated by statistical analysis to screen potential biomarkers. After that, potential biomarkers were validated by enzyme-linked immunosorbent assay (ELISA) and diagnostic models were also established for observation of multi-index diagnostic efficacy.
118 differential expressed proteins (DEPs) were obtained in serum after statistical analysis. After the diagnostic efficacy evaluation and clinical verification, inter-alpha-trypsin inhibitor heavy chain H2 (ITIH2), complement factor H-related protein 2 (CFHR2), complement factor H-related protein 3 (CFHR3), and complement factor H-related protein 5 (CFHR5) were found as potential biomarkers, with 0.7167 (95 %CI: 0.5846-0.8487), 0.8600 (95 %CI: 0.7701-0.9499), 0.8150 (95 %CI: 0.6998-0.9302), and 0.9978 (95 %CI: 0.9918-1.0040) AUC value, respectively. The remaining DEPs except CFHR5 were constructed as diagnostic models, the diagnostic model contained CFHR2 and CFHR3 had good diagnostic efficacy with 0.942 (95 %CI: 0.872-0.980) AUC value compared to other models.
This study provides a reference for the discovery of serum protein markers for osteoarticular tuberculosis diagnosis, and the screened DEPs can also provide directions for subsequent pathogenesis research.
骨关节结核是肺外结核（EPTB）疾病之一，主要由结核分枝杆菌（MTB）感染骨与关节所致。当前临床试验方法的局限性导致误诊率较高，影响治疗及预后。本研究旨在寻找可辅助诊断骨关节结核的血清生物标志物。
蛋白质组学可作为发现疾病生物标志物的重要方法。采用液相色谱-串联质谱（LC-MS/MS）分析2020年6月至2021年12月收集的90份血清样本中的蛋白质，然后通过统计分析进行评估以筛选潜在生物标志物。之后，通过酶联免疫吸附测定（ELISA）对潜在生物标志物进行验证，并建立诊断模型以观察多指标诊断效能。
经统计分析，血清中获得118种差异表达蛋白（DEP）。经过诊断效能评估及临床验证，发现α-胰蛋白酶抑制剂重链H2（ITIH2）、补体因子H相关蛋白2（CFHR2）、补体因子H相关蛋白3（CFHR3）和补体因子H相关蛋白5（CFHR5）为潜在生物标志物，其曲线下面积（AUC）值分别为0.7167（95%置信区间：0.5846 - 0.8487）、0.8600（95%置信区间：0.7701 - 0.9499）、0.8150（95%置信区间：0.6998 - 0.9302）和0.9978（95%置信区间：0.9918 - 1.0040）。除CFHR5外的其余DEP构建诊断模型，包含CFHR2和CFHR3的诊断模型诊断效能良好，与其他模型相比，AUC值为0.942（95%置信区间：0.872 - 0.980）。
本研究为骨关节结核诊断血清蛋白标志物的发现提供了参考，筛选出的DEP也可为后续发病机制研究提供方向。
