结核分枝杆菌游离DNA检测在肺外结核诊断中的价值

Value of Mycobacterium tuberculosis cell-free DNA detection in the diagnosis of extrapulmonary tuberculosis

目的探讨结核分枝杆菌(MTB)游离DNA(cfDNA)检测技术在肺外结核诊断中的应用价值。方法选取2021年7月至2022年12月该院收治的高度疑似肺外结核患者266例作为研究对象,根据临床诊断结果,分为肺外结核组117例和非结核组149例。所有患者均采集脑脊液、胸腔积液、尿液及血液标本,并同时进行MTB cfDNA检测、结核分枝杆菌及利福平耐药快速检测(GeneXpert MTB/RIF)、涂片抗酸染色及血液标本结核感染T细胞γ干扰素释放试验(TB-IGRA)。通过分析4种检测方法的效能指标评估MTB cfDNA检测技术在肺外结核病诊断中的临床价值。结果MTB cfDNA检测法对脑脊液、胸腔积液、尿液中MTB的检出率均显著高于涂片抗酸染色(χ^(2)=5.714、9.289、9.226,P=0.017、0.002、0.002)。虽然MTB cfDNA检测法对脑脊液、尿液中MTB的检出率高于GeneXpert MTB/RIF,但差异无统计学意义(χ^(2)=0.143,P=0.705;χ^(2)=0.648,P=0.421);MTB cfDNA检测法对胸腔积液中MTB的检出率显著高于GeneXpert MTB/RIF(χ^(2)=4.222,P=0.040)。在肺外结核组,MTB cfDNA检测法的MTB检出率为26.50%(31/117),显著高于GeneXpert MTB/RIF[15.38%(18/117)]和涂片抗酸染色[3.42%(4/117)],差异均有统计学意义(χ^(2)=4.362,P=0.037;χ^(2)=24.492,P<0.05);而TB-IGRA的MTB检出率为72.65%(85/117),显著高于MTB cfDNA检测(χ^(2)=49.850,P<0.001)。MTB cfDNA检测法的灵敏度、特异度、阳性预测值、阴性预测值分别为26.50%、100.00%、100.00%、63.40%,其灵敏度显著高于GeneXpert MTB/RIF(15.38%)和涂片抗酸染色(3.42%),但低于TB-IGRA(72.65%),差异均有统计学意义(P<0.05)。结论MTB cfDNA检测在肺外结核诊断中具有较高的灵敏度及特异度,故MTB cfDNA检测在肺外结核诊断中具有较好的应用前景。

Objective To investigate the clinical application value of Mycobacterium tuberculosis cell-free DNA(MTB cfDNA)detection technology in the diagnosis of extrapulmonary tuberculosis.Methods A total of 266 patients with highly suspected extrapulmonary tuberculosis were enrolled in the Hospital from July 2021 to December 2022,and divided into extrapulmonary tuberculosis group of 117 cases and non-tuberculosis group of 149 cases according to the results of clinical diagnosis.Cerebrospinal fluid,pleural effusion,urine and blood samples were collected from all patients,and MTB cfDNA detection,GeneXpert MTB/RIF,antacid staining and TB-IGRA were performed simultaneously.The clinical value of MTB cfDNA detection technology in the diagnosis of extrapulmonary tuberculosis was assessed by analyzing the efficacy indexes of the four testing methods.Results The detection rates of MTB by MTB cfDNA detection were significantly higher in cerebrospinal fluid,pleural effusion and urine than those by antacid staining(χ^(2)=5.714,9.289,9.226,P=0.017,0.002,0.002).Although the detection rates of MTB by MTB cfDNA were higher than those by GeneXpert MTB/RIF in cerebrospinal fluid and urine,the differences were not statistically significant(χ^(2)=0.143,P=0.705;χ^(2)=0.648,P=0.421);the detection rate of MTB by MTB cfDNA in pleural effusion was significantly higher than that by GeneXpert MTB/RIF(χ^(2)=4.222,P=0.040).In the extrapulmonary tuberculous group,the MTB detection rate by MTB cfDNA test was 26.50%(31/117),which was significantly higher than that of GeneXpert MTB/RIF[15.38%(18/117)]and antacid staining[3.42%(4/117)],with statistically significant differences(χ^(2)=4.362,P=0.037;χ^(2)=24.492,P<0.05);while the MTB detection rate of TB-IGRA test was 72.65%(85/117),which was significantly higher than that of MTB cfDNA test(χ^(2)=49.850,P<0.001).The sensitivity,specificity,positive predictive value and negative predictive value of MTB cfDNA detection were 26.50%,100.00%,100.00%,and 63.40%,respectively.The sensitivity of MTB cfDNA detection was significantly higher than that 15.38%of GeneXpert MTB/RIF and 3.42%of antacid staining,and lower than 72.65%of TB-IGRA,the differences had statistical significance(P<0.05).Conclusion MTB cfDNA detection exhibits high sensitivity and specificity in the diagnosis of extrapulmonary tuberculosis,and it has good application prospect in the diagnosis of extrapulmonary tuberculosis.