尿液脂阿拉伯甘露聚糖抗原检测对肺外结核的诊断价值

doi:10.19982/j.issn.1000-6621.20240383

摘要/Abstract

摘要：

目的: 探讨尿液脂阿拉伯甘露聚糖(lipoarabinomannan, LAM)抗原检测对肺外结核患者的诊断价值。方法: 连续收集2023年4月至2024年6月于杭州市红十字会医院就诊的92例疑似肺外结核患者的尿液样本进行LAM抗原检测,且对相应病灶部位样本进行GeneXpert MTB/RIF(简称“Xpert”)检测。以临床综合诊断为参考标准,比较两种方法单独及联合检测对肺外结核的诊断效能。结果: 以临床综合诊断结果为标准,尿液LAM抗原和Xpert检测肺外结核的敏感度、特异度和受试者工作特征曲线下面积(area under curve, AUC)分别为49.3%(95%CI:36.8%~61.8%)、92.0%(95%CI:74.0%~99.0%)、0.706(95%CI:0.602~0.797)和49.3%(95%CI:36.8%~61.8%)、100.0%(95%CI:86.3%~100.0%)、0.746(95%CI:0.645~0.831)。尿液LAM抗原联合Xpert检测肺外结核的敏感度为73.1%(95%CI:60.9%~83.2%),高于尿液LAM抗原检测和Xpert检测,差异均有统计学意义(χ²=27.672,P<0.001;χ²=17.576,P<0.001);AUC为0.826(95%CI:0.733~0.897),高于尿液LAM抗原检测和Xpert检测,差异均有统计学意义(Z=1.602,P<0.001;Z=4.175,P=0.037)。结论: 尿液LAM抗原检测在肺外结核的诊断中具有一定的应用前景,联合Xpert可以提高检测的敏感度,提升在肺外结核诊断中的应用价值。

关键词: 肺外结核, 尿, 甘露聚糖类, 核酸扩增技术, 诊断

Abstract:

Objective: To explore the diagnostic value of urinary lipoarabinomannan (LAM) antigen detection in patients with extrapulmonary tuberculosis. Methods: Urine samples of 92 suspected patients with extra pulmonary tuberculosis treated in Hangzhou Red Cross Hospital from April 2023 to June 2024 were continuously collected for LAM antigen detection, and GeneXpert MTB/RIF (Xpert) test detection was performed on the corresponding lesion site samples. Taking the clinical comprehensive diagnosis as the reference standard, the diagnostic efficiency of the two methods alone and in combination for extrapulmonary tuberculosis was compared. Results: Based on the comprehensive clinical diagnosis results, the sensitivity, specificity and area under curve (AUC) of urine LAM antigen and Xpert for the test of extrapulmonary tuberculosis were 49.3% (95%CI: 36.8%-61.8%), 92.0% (95%CI: 74.0%-99.0%), 0.706 (95%CI: 0.602-0.797) and 49.3% (95%CI: 36.8%-61.8%), 100.0% (95%CI: 86.3%-100.0%), 0.746 (95%CI: 0.645-0.831), respectively. The sensitivity of urine LAM antigen combined with Xpert to detect extrapulmonary tuberculosis was 73.1% (95%CI: 60.9%-83.2%), which was higher than that of urine LAM antigen (χ²=27.672, P<0.001) and Xpert (χ²=17.576, P<0.001). The AUC was 0.826 (95%CI: 0.733-0.897), which was higher than that of urine LAM antigen and Xpert detection; and the differences were statistically significant (Z=1.602, P<0.001; Z=4.175, P=0.037). Conclusion: Urine LAM antigen detection has a certain application prospect in the diagnosis of extrapulmonary tuberculosis, and the combination with Xpert can improve the sensitivity of detection and enhance the application value in the diagnosis of extrapulmonary tuberculosis.

Key words: Tuberculosis, extrapulmonary, Urine, Mannans, Nucleic acid amplification techniques, Diagnosis

中图分类号:

R52
R446

朱明智, 邵燕琴, 范大鹏, 刘立宾, 梅宾, 戴玲珊, 蔡龙. 尿液脂阿拉伯甘露聚糖抗原检测对肺外结核的诊断价值[J]. 中国防痨杂志, 2025, 47(4): 471-476. doi: 10.19982/j.issn.1000-6621.20240383

Zhu Mingzhi, Shao Yanqin, Fan Dapeng, Liu Libin, Mei Bin, Dai Lingshan, Cai Long. Diagnostic value of urine lipoarabinomannan antigen detection in extrapulmonary tuberculosis[J]. Chinese Journal of Antituberculosis, 2025, 47(4): 471-476. doi: 10.19982/j.issn.1000-6621.20240383

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参考文献 29

[1]	Muneer A, Macrae B, Krishnamoorthy S, et al. Urogenital tuberculosis-epidemiology, pathogenesis and clinical features. Nat Rev Urol, 2019, 16(10):573-598. doi:10.1038/s41585-019-0228-9. pmid: 31548730
[2]	胡鑫洋, 高静韬. 世界卫生组织《2024年全球结核病报告》解读. 结核与肺部疾病杂志, 2024, 5(6): 500-504. doi:10.19983/j.issn.2096-8493.2024164.
[3]	Baykan AH, Sayiner HS, Aydin E, et al. Extrapulmonary tuberculosis: an old but resurgent problem. Insights Imaging, 2022, 13(1): 39. doi:10.1186/s13244-022-01172-0.
[4]	刘燕飞, 李涛, 夏愔愔, 等. 2018—2020年结核病定点医院肺外结核和结核性胸膜炎患者次均住院费用及影响因素分析. 中国防痨杂志, 2024, 46(5): 509-518. doi:10.19982/j.issn.1000-6621.20230376.
[5]	刘燕飞, 李涛, 夏愔愔, 等. 2018—2020年9家结核病定点医院肺外结核病住院患者特征分析. 疾病监测, 2023, 38(10): 1223-1228. doi:10.3784/jbjc.202212260551.
[6]	Sigal GB, Pinter A, Lowary TL, et al. A Novel Sensitive Immunoassay Targeting the 5-Methylthio-d-Xylofuranose-Lipoarabinomannan Epitope Meets the WHO’s Performance Target for Tuberculosis Diagnosis. J Clin Microbiol, 2018, 56(12): e01338-18. doi:10.1128/JCM.01338-18.
[7]	Correia-Neves M, Fröberg G, Korshun L, et al. Biomarkers for tuberculosis: the case for lipoarabinomannan. ERJ Open Res, 2019, 5(1): 00115-2018. doi:10.1183/23120541.00115-2018.
[8]	Bulterys MA, Wagner B, Redard-Jacot M, et al. Point-Of-Care Urine LAM Tests for Tuberculosis Diagnosis: A Status Update. J Clin Med, 2019, 9(1): 111. doi:10.3390/jcm9010111.
[9]	Lyu M, Zhou Y, Chen Y, et al. Exploring the eligibility of all reported lipoarabinomannan-testing assays in different clinical situations: a systematic review and meta-analysis of 97 articles. Int J Infect Dis, 2022, 125: 19-34. doi:10.1016/j.ijid.2022.10.015. pmid: 36244601
[10]	Bjerrum S, Broger T, Székely R, et al. Diagnostic Accuracy of a Novel and Rapid Lipoarabinomannan Test for Diagnosing Tuberculosis Among People With Human Immunodeficiency Virus. Open Forum Infect Dis, 2019, 7(1): ofz530. doi:10.1093/ofid/ofz530.
[11]	Minion J, Leung E, Talbot E, et al. Diagnosing tuberculosis with urine lipoarabinomannan: systematic review and meta-analysis. Eur Respir J, 2011, 38(6): 1398-1405. doi:10.1183/09031936.00025711. pmid: 21700601
[12]	Broger T, Nicol MP, Sigal GB, et al. Diagnostic accuracy of 3 urine lipoarabinomannan tuberculosis assays in HIV-negative outpatients. J Clin Invest, 2020, 130(11): 5756-5764. doi:10.1172/JCI140461.
[13]	Huerga H, Bastard M, Lubega AV, et al. Novel FujiLAM assay to detect tuberculosis in HIV-positive ambulatory patients in four African countries: a diagnostic accuracy study. Lancet Glob Health, 2023, 11(1): e126-e135. doi:10.1016/S2214-109X(22)00463-6. pmid: 36521944
[14]	Peng L, Dai L, Zhu M, et al. Developing a method to detect lipoarabinomannan in pleural fluid and assessing its diagnostic efficacy for tuberculous pleural effusion. Heliyon, 2023, 9(8): e18949. doi:10.1016/j.heliyon.2023.e18949.
[15]	中华人民共和国国家卫生和计划生育委员会. WS 288—2017肺结核诊断. 结核与肺部疾病杂志, 2024, 5(4): 376-378. doi:10.19983/j.issn.2096-8493.2024022.
[16]	中华人民共和国国家卫生和计划生育委员会. WS 196—2017结核病分类. 结核与肺部疾病杂志, 2024, 5(4): 379-380. doi:10.19983/j.issn.2096-8493.2024055.
[17]	刘喆, 赵强, 张樱, 等. 实时荧光定量核酸扩增技术在结核筛查诊断中的临床应用研究. 中华医院感染学杂志, 2019, 29(23): 3535-3538. doi:10.11816/cn.ni.2019-190103.
[18]	Kohli M, Schiller I, Dendukuri N, et al. Xpert MTB/RIF assay for extrapulmonary tuberculosis and rifampicin resis-tance. Cochrane Database Syst Rev, 2018, 8(8): CD012768. doi:10.1002/14651858.CD012768.pub2.
[19]	Lee MK, Moon C, Lee MJ, et al. Risk factors for the delayed diagnosis of extrapulmonary TB. Int J Tuberc Lung Dis, 2021, 25(3): 191-198. doi:10.5588/ijtld.20.0788. pmid: 33688807
[20]	孙金昊, 陶磊, 贺向红, 等. Gene Xpert MTB/RIF系统、MGIT-960快速培养系统及药敏检测肺结核患者痰标本、支气管肺泡灌洗液标本阳性率比较及耐药分析. 临床军医杂志, 2022, 50(12): 1275-1277, 1281. doi:10.16680/j.1671-3826.2022.12.19.
[21]	席素雅, 刘薇, 乔庆哲, 等. 白细胞介素-27、腺苷脱氢酶、基因检测、结核杆菌培养对结核性胸腔积液诊断价值研究. 临床军医杂志, 2023, 51(2): 173-175. doi:10.16680/j.1671-3826.2023.02.17.
[22]	董裕, 张福真, 尚媛媛, 等. GeneXpert MTB/RIF Ultra在肺外结核诊断中的研究进展. 中国防痨杂志, 2023, 45(12): 1193-1197. doi:10.19982/j.issn.1000-6621.20230357.
[23]	张天辉, 马子淳, 刘荣梅, 等. 基于尿液的脂阿拉伯甘露聚糖抗原检测对肺结核的诊断价值. 中华结核和呼吸杂志, 2024, 47(2): 132-136. doi:10.3760/cma.j.cn112147-20230814-00074.
[24]	Gao M, Wu Q, Wang X, et al. Advancements in LAM-based diagnostic kit for tuberculosis detection: enhancing TB diagnosis in HIV-negative individuals. Front Microbiol, 2024, 15: 1367092. doi:10.3389/fmicb.2024.1367092.
[25]	Li TX, Wang J, Yang YS, et al. Evaluation of Xpert MTB/RIF assay for the diagnosis of extrapulmonary tuberculosis in Southwest China. PLoS Negl Trop Dis, 2023, 17(6): e0011403. doi:10.1371/journal.pntd.0011403.
[26]	Cox JA, Lukande RL, Kalungi S, et al. Is Urinary Lipoarabinomannan the Result of Renal Tuberculosis? Assessment of the Renal Histology in an Autopsy Cohort of Ugandan HIV-Infected Adults. PLoS One, 2015, 10(4): e0123323. doi:10.1371/journal.pone.0123323.
[27]	Moule MG, Cirillo JD. Mycobacterium tuberculosis Dissemination Plays a Critical Role in Pathogenesis. Front Cell Infect Microbiol, 2020, 10: 65. doi:10.3389/fcimb.2020.00065.
[28]	Rodriguez-Takeuchi SY, Renjifo ME, Medina FJ. Extrapulmonary Tuberculosis: Pathophysiology and Imaging Findings. Radiographics, 2019, 39(7): 2023-2037. doi:10.1148/rg.2019190109. pmid: 31697616
[29]	MacLean E, Pai M. Urine Lipoarabinomannan for Tuberculosis Diagnosis: Evolution and Prospects. Clin Chem, 2018, 64(8): 1133-1135. doi:10.1373/clinchem.2018.286625. pmid: 29632129

资料	合计(92例)	EPTB患者(67例)	非EPTB患者(25例)	χ²值	P值
性别				4.109	0.043
男性	43	27(40.3)	16(64.0)
女性	49	40(59.7)	9(36.0)
年龄组				8.422	0.015
<30岁	11	11(16.4)	0(0.0)
30~59岁	48	37(55.2)	11(44.0)
≥60岁	33	19(28.4)	14(56.0)
样本来源				2.213	0.497
淋巴结	40	33(49.4)	7(28.0)
骨与关节	16	8(11.9)	8(32.0)
心包	14	9(13.4)	5(20.0)
泌尿生殖系统	11	9(13.4)	2(8.0)
其他来源^a	11	8(11.9)	3(12.0)
肺外样本类型				6.806	0.132
组织	49	35(52.3)	14(56.0)
脓液	14	12(17.9)	2(8.0)
尿液	10	8(11.9)	2(8.0)
其他类型^b	19	12(17.9)	7(28.0)

类别	综合诊断患者		敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)
类别	EPTB(67例)	非EPTB(25例)	敏感度 (%,95%CI)	特异度 (%,95%CI)	阳性预测值 (%,95%CI)	阴性预测值 (%,95%CI)
LAM			49.3 (36.8~61.8)	92.0 (74.0~99.0)	94.3 (81.0~98.5)	40.4 (34.2~46.8)
阳性	33	2^a
阴性	34	23
Xpert			49.3 (36.8~61.8)	100.0 (86.3~100.0)	100.0 (89.4~100.0)	42.4 (36.7~48.2)
阳性	33	0
阴性	34	25
LAM+Xpert			73.1 (60.9~83.2)	92.0 (74.0~99.0)	96.1 (86.5~98.9)	56.1 (45.8~65.9)
阳性	49	2^a
阴性	18	23

方法	AUC值	95%CI值	Z值	P值
LAM	0.706	0.602~0.797	0.788^a	0.431^a
Xpert	0.746	0.645~0.831	4.175^b	0.037^b
LAM+Xpert	0.826	0.733~0.897	1.602^c	<0.001^c