血浆生物标志物MMP-8在预测活动性肺结核病诊断效能的评价

Evaluation of the diagnostic efficacy of plasma biomarker MMP-8 in predicting active pulmonary tuberculosis

目的本研究以结核菌多肽蛋白刺激全血细胞,建立化学发光技术检测血浆中基质金属蛋白酶8(MMP-8)的表达水平,评价其区分活动性结核的诊断价值。方法通过结核菌特异性多肽体外刺激全血并分离血浆,用化学发光技术检测不同人群中血浆MMP-8表达水平的差异。结果建立化学发光方法检测血浆生物标志物MMP-8的表达水平,受试者工作特征(ROC)曲线分析显示,在区分痰涂片阳性肺结核(AFB+TB)患者和健康对照(HC)者中曲线下面积(AUC)为0.95(95%CI:0.92~0.98),准确度0.85,灵敏度为0.94,特异度为0.83。在区分痰涂片阴性肺结核(AFB-TB)患者和HC对照组AUC为0.89(95%CI:0.85~0.094),准确度0.76,灵敏度为0.94,特异度为0.76。鉴别AFB+TB和结核潜伏感染(LTBI)者AUC为0.96(95%CI:0.94~0.98),灵敏度0.83,特异度为0.98。区分AFB-TB和LTBI者的AUC为0.93(95%CI:0.90~0.97),灵敏度为0.76,特异度为0.98。TB-DNA、痰结核菌培养、γ-干扰素释放试验(IGRAs)和MMP-8方法对AFB+TB患者的检出率分别为79.17%、52.08%、83.33%和85.42%。在AFB-TB的检出率分别为21.05%、15.79%、61.05%和75.78%。同时平行比较MMP-8和TB-DNA、痰培养、IGRAs 3种方法在AFB-TB患者阳性率,其各组间差异有统计学意义(P<0.05)。结论化学发光检测血浆生物标志物MMP-8可辅助预测活动性结核病的诊断,尤其在涂阴结核中预测具有显著优势和参考价值。

Objective To evaluate the diagnostic value of matrix metalloproteinase 8(MMP-8)in differentiating active tuberculosis though the whole blood cells stimulated by tuberculin polypeptide protein were used to establish a chemiluminescence technique to detect the expression level of MMP-8 in plasma.Methods The whole blood was stimulated by tubercular specific peptides in vitro and plasma was separated.The expression of MMP-8,a biomarker in plasma,was detected by chemiluminescence technique in different populations.Results A chemiluminescence method was established to detect the expression level of the plasma biomarker MMP-8,and the ROC curve analysis showed that the AUC was 0.95(95%CI:0.92-0.98),the accuracy was 0.85,the sensitivity was 0.94,and the specificity was 0.95 in distinguishing AFB+TB from HC controls.In distinguishing phlegm smear negative pulmonary tuberculosis patients(AFB-TB)from HC control group,the AUC was 0.89(95%CI:0.85-0.094),the accuracy was 0.76,the sensitivity was 0.94,and the specificity was 0.76.The AUC for distinguishing AFB-TB from latent infection of tuberculosis(LTBI)was 0.96(95%CI:0.94-0.98),the sensitivity was 0.83,and the specificity was 0.98.The AUC for distinguishing AFB+TB from LTBI was 0.93(95%CI:0.90-0.97),the sensitivity was 0.76,and the specificity was 0.98.The detection rates of TB-DNA,sputum tuberculosis culture,interferon gamma release assay(IGRAs)and MMP-8 in patients with active smear-positive tuberculosis were 79.17%,52.08%,83.33%and 85.42%,respectively.The detection rates of smear-negative tuberculosis patients were 21.05%,15.79%,61.05%and 75.78%,respectively.At the same time,the positive rates of MMP-8 and TB-DNA,sputum culture,and IGRAs in smear-negative tuberculosis patients were compared in parallel,and the differences among the groups were significant and statistically significant(P<0.05).Conclusion The data show that chemiluminescent detection of plasma biomarker MMP-8 can assist in predicting the diagnosis of active tuberculosis,especially in smear-negative tuberculosis,which has significant advantages and reference value.