Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis A Tuberculosis Network European Trialsgroup Study
Bronchoalveolar Lavage Enzyme-linked Immunospot for a Rapid Diagnosis of Tuberculosis A Tuberculosis Network European Trialsgroup Study
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DOI：
10.1164/rccm.200904-0557oc
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发表时间：
2009-10-01
影响因子：
24.7
通讯作者：
Lange, Christoph
中科院分区：
文献类型：
--
作者：
Jafari, Claudia;Thijsen, Steven;Lange, Christoph
基本原理：当痰涂片中不能检测到抗酸杆菌（AFB）时，肺结核（TB）的快速诊断是困难的。目的：根据原理研究的证明，我们在常规临床实践中检查是否可以通过用结核分枝杆菌特异性酶联免疫斑点（ELISpot）测定进行局部免疫诊断来区分痰AFB涂片阴性TB的个体与潜伏性TB感染的个体。方法：无法产生痰液或痰涂片呈AFB阴性的疑似活动性TB受试者前瞻性入组欧洲结核病网络试验组中心。用早期分泌抗原靶6和培养滤液蛋白10肽对外周血单个核细胞（PBMC）和支气管肺泡灌洗单个核细胞（BALMCs）进行ELISpot。M.对支气管肺泡灌洗液进行结核特异性核酸扩增（NAAT）。347例患者中有71例（20.4%）患有活动性结核病。在276例有其他诊断的患者中，127例（46.0%）被认为是潜伏感染M。PBMC ELI Spot检测结果为阳性。BALMC ELISpot诊断活动性肺结核的敏感性和特异性分别为91%和80%。BALMC ELISpot（诊断优势比[OR]，40.4）上级PBMC ELISpot（OR，10.0）、结核菌素皮肤试验（OR，7.8）和M.结核特异性NAAT（OR，12.4）诊断痰AFB涂片阴性TB。BALMC ELISpot与PBMC ELISpot和结核菌素皮试相比，不受结核病史的影响。结论支气管肺泡灌洗ELISpot是临床上快速鉴别痰AFB涂阴结核和潜伏性结核感染的重要方法。
Rationale: The rapid diagnosis of pulmonary tuberculosis (TB) is difficult when acid fast bacilli (AFB) cannot be detected in sputum smears.Objectives: Following a proof of principle study, we examined in routine clinical practice whether individuals with sputum AFB smear-negative TB can be discriminated from those with latent TB infection by local immunodiagnosis with a Mycobacterium tuberculosis-specific enzyme-linked immunospot (ELISpot) assay.Methods: Subjects suspected of having active TB who were unable to produce sputum or with AFB-negative sputum smears were prospectively enrolled at Tuberculosis Network European Trialsgroup centers in Europe. ELISpot with early-secretory-antigenic-target-6 and culture-filtrate-protein-10 peptides was performed on peripheral blood mononuclear cells (PBMCs) and bronchoalveolar lavage mononuclear cells (BALMCs). M. tuberculosis-specific nucleic acid amplification (NAAT) was performed on bronchoalveolar lavage fluid.Measurements and Main Results. Seventy-one of 347 (20.4%) patients had active TB. Out of 276 patients who had an alternative diagnosis, 127 (46.0%) were considered to be latently infected with M. tuberculosis by a positive PBMC ELI Spot result. The sensitivity and specificity of BALMC ELISpot for the diagnosis of active pulmonary TB were 91 and 80%, respectively. The BALMC ELISpot (diagnostic odds ratio [OR], 40.4) was superior to PBMC ELISpot (OR, 10.0), tuberculin skin test (OR, 7.8), and M. tuberculosis specific NAAT (OR, 12.4) to diagnose sputum AFB smear-negative TB. In contrast to PBMC ELISpot and tuberculin skin test, the BALMC ELISpot was not influenced by previous history of TB.Conclusions Bronchoalveolar lavage ELISpot is an important advancement to rapidly distinguish sputum AFB smear-negative TB from latent TB infection in routine clinical practice.