基于特异性配体蛋白SMAD2检测法用于活动性结核病的诊断价值研究

doi:10.19982/j.issn.1000-6621.20250028

摘要/Abstract

摘要：

目的: 分析基于SMAD2配体蛋白捕捉多种结核抗原的检测方法(简称“SMAD2方法”)对活动性结核病的诊断价值。方法: 选取2023年1—3月就诊于首都医科大学附属北京胸科医院的活动性结核病患者152例,进行结核分枝杆菌痰涂片、痰培养、荧光PCR检测等结核病相关检查,并选取同时期进行健康体检者177名作为研究对象。基于SMAD2配体蛋白捕捉多种结核抗原的特性,利用酶联免疫吸附试验(ELISA)方法检测活动性结核病患者及健康对照人群血清中的结核抗原含量(用A₄₅₀值表示),采用受试者工作特征(receiver operating characteristic,ROC)曲线分析其诊断结核病的价值。结果: 结核病组和健康对照组的结核抗原含量分别为0.589(0.426,0.807)和0.257(0.209,0.340),两者差异有统计学意义(Z=13.050,P<0.001)。ROC曲线分析结果显示,SMAD2方法区分结核病患者与健康对照人群的曲线下面积(area under curve,AUC)为0.917(95%CI:0.889~0.946);最大约登指数下的诊断敏感度为90.13%(95%CI:84.36%~93.93%),特异度为78.53%(95%CI:71.91%~83.94%)。SMAD2方法诊断结核病的阳性预测值为78.29%(137/175)、阴性预测值为90.26%(139/154),准确率为83.89%(276/329),误诊率为21.47%(38/177),漏诊率为9.87%(15/152)。菌阳患者、菌阴患者的阳性检出率分别为90.37%(122/135)、88.24%(15/17),两者差异无统计学意义(χ²=0.077,P=0.781),PCR阳性患者、PCR阴性患者的阳性检出率分别为88.18%(97/110)、95.24%(40/42),两者差异无统计学意义(χ²=1.702,P=0.192)。结论: SMAD2方法对于活动性结核病尤其是菌阴结核病的诊断具有潜在的辅助诊断价值。

关键词: Smad2蛋白质, 分枝杆菌, 结核, 抗原, 诊断

Abstract:

Objective: The specific ligand protein SMAD2 was used to detect multiple tuberculosis antigens in patients, we aim to explore its diagnostic value for active tuberculosis. Methods: 152 tuberculosis patients who were admitted to Beijing Chest Hospital affiliated to Capital Medical University from January to March, 2023 were selected for tuberculosis-related examinations such as sputum smear, sputum culture and fluorescence PCR, and 177 healthy people receiving health checkup at the same time were selected as research objects. Based on SMAD2 ligand protein’s characteristic of capturing multiple tuberculosis antigens, a specially designed enzyme-linked immunosorbent assay (ELISA) was used to detect the content of tuberculosis antigen (expressed by A₄₅₀) in the serum of tuberculosis patients and healthy controls, and receiver operating characteristic (ROC) curve was used to analyze its diagnostic value. Results: The content of tuberculosis antigen in tuberculosis patients and healthy controls were 0.589 (0.426,0.807) and 0.257 (0.209,0.340) respectively, and the difference was statistically significant (Z=13.050, P<0.001). The results of ROC curve analysis showed that the AUC of SMAD2-based detection method for distinguishing tuberculosis patients from healthy people was 0.917 (95%CI: 0.889-0.946), the diagnostic sensitivity under the maximum Yoden Index was 90.13% (95%CI:84.36%-93.93%), and the specificity was 78.53% (95%CI:71.91%-83.94%). The positive and negative predictive value were 78.29% (137/175) and 90.26% (139/154), respectively. The accuracy rate was 83.89% (276/329), the misdiagnosis rate was 21.47% (38/177), and the missed diagnosis rate was 9.87% (15/152). The positive detection rates of bacteriologically positive and negative patients were 90.37% (122/135) and 88.24% (15/17) respectively, with no statistical significance difference between them (χ²=0.077, P=0.781). The positive detection rates of PCR positive and negative patients were 88.18% (97/110) and 95.24% (40/42) respectively, with no statistical significance difference between them (χ²=1.702, P=0.192). Conclusion: The SMAD2-based detection method has potential value for auxiliary diagnosis of active tuberculosis, especially for bacteriologically negative tuberculosis.

Key words: Smad2 protein, Mycobacterium tuberculosis, Antigen, Diagnosis

中图分类号:

谢忠尧, 张慕丽, 曹廷明, 曹洋, 孙照刚. 基于特异性配体蛋白SMAD2检测法用于活动性结核病的诊断价值研究[J]. 中国防痨杂志, 2025, 47(6): 694-700. doi: 10.19982/j.issn.1000-6621.20250028

Xie Zhongyao, Zhang Muli, Cao Tingming, Cao Yang, Sun Zhaogang. Research on the diagnostic value of specific ligand protein SMAD2-based detection method for active tuberculosis[J]. Chinese Journal of Antituberculosis, 2025, 47(6): 694-700. doi: 10.19982/j.issn.1000-6621.20250028

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因素	组别		敏感度 [%(95%CI)]	特异度 [%(95%CI)]	阳性预测值(%)	阴性预测值(%)	准确率 (%)	误诊率 (%)	漏诊率 (%)
因素	结核病 (152例)	对照组 (177名)	敏感度 [%(95%CI)]	特异度 [%(95%CI)]	阳性预测值(%)	阴性预测值(%)	准确率 (%)	误诊率 (%)	漏诊率 (%)
SMAD2方法			90.13 (84.36~93.93)	78.53 (71.91~83.94)	78.29	90.26	83.89	21.47	9.87
阳性	137	38
阴性	15	139
痰培养			88.82 (82.82~92.90)	100.00 (97.88~100.00)	1.00	91.24	94.83	0	11.18
阳性	135	0
阴性	17	177
痰涂片			32.24 (25.32~40.03)	100.00 (97.88~100.00)	1.00	63.21	68.69	0	67.76
阳性	49	0
阴性	103	177
PCR			72.37 (64.77~78.86)	98.87 (95.97~99.80)	98.21	80.65	86.63	11.30	27.63
阳性	110	2
阴性	42	175

因素	敏感度[%(95%CI)]	特异度[%(95%CI)]
最大约登指数	90.13(84.36~93.93)	78.53(71.90~83.90)
WHO目标产品目录结核病分诊实验最低敏感度(90%)	90.00(84.36~93.93)	79.01(72.00~84.01)
WHO目标产品目录结核病分诊实验最低特异度(70%)	92.76(87.51~95.91)	70.00(62.94~76.32)
WHO目标产品目录结核病确认实验最低敏感度(65%)	65.00(57.27~72.25)	92.66(87.84~95.66)
WHO目标产品目录结核病确认实验最低特异度(98%)	50.66(42.79~58.49)	98.00(94.33~99.12)