The extremely slow growth rate of Mycobacterium tuberculosis (Mtb) challenges traditional methods for tuberculosis (TB) diagnosis. Here, we assessed the efficacy of a previously developed Mtb antigen-specific gamma interferon (IFN-γ) enzyme-linked immunospot (ELISPOT) performed on bronchoalveolar lavage fluid (BALF) from a cohort of 414 patients including 333 PTB patients (202/333 were sputum culture positive) for the diagnosis of PTB. We could confirm that antigen-specific IFN-γ-producing CD4+ T cells were concentrated significantly in BALF mononuclear cells (BALMC) compared with that in peripheral blood mononuclear cells (PBMC) assayed in parallel, but not those of CD8+ T cells both in sputum culture-negative and positive PTB. The magnitude of IFN-γ responses in the BALF was associated with bacterial load, and 9/202 of PTB with endobronchial TB (EBTB) were slightly reduced by the anti-TB treatment. Moreover, antigen-specific IFN-γ ELISPOT performed on BALMC showed higher sensitivity than PBMC ELISPOT. In addition, the differences of the BALMC ELISPOT between PTB and PTB with diabetes were not found, whereas PBMC IFN-γ responses were decreased in PTB with diabetes. Combined with the microbiological detection in BALF, such as microscopy and culture, the BALMC ELISPOT offers the opportunity for the more accurate diagnosis of PTB, especially those with clinical comorbidities.

中文翻译：

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支气管肺泡灌洗液中抗原特异性 IFN-γ 反应升高，不受临床合并症影响，可改善肺结核诊断

结核分枝杆菌 (Mtb) 极其缓慢的生长速度挑战了传统的结核病 (TB) 诊断方法。在这里，我们评估了先前开发的 Mtb 抗原特异性 γ 干扰素 (IFN-γ) 酶联免疫斑点 (ELISPOT) 对来自 414 名患者的支气管肺泡灌洗液 (BALF) 的疗效，其中包括 333 名 PTB 患者 (202/333痰培养阳性）用于 PTB 的诊断。我们可以证实，与平行测定的外周血单核细胞 (PBMC) 相比，BALF 单核细胞 (BALMC) 中产生抗原特异性 IFN-γ 的 CD4+ T 细胞显着集中，但不是痰中的 CD8+ T 细胞培养阴性和阳性 PTB。BALF 中 IFN-γ 反应的大小与细菌负荷有关，和 9/202 合并支气管内 TB (EBTB) 的 PTB 通过抗 TB 治疗略有减少。此外，在 BALMC 上进行的抗原特异性 IFN-γ ELISPOT 显示出比 PBMC ELISPOT 更高的灵敏度。此外，未发现 PTB 和患有糖尿病的 PTB 之间 BALMC ELISPOT 的差异，而患有糖尿病的 PTB 中 PBMC IFN-γ 反应降低。结合 BALF 中的微生物检测，如显微镜和培养，BALMC ELISPOT 为更准确地诊断 PTB，尤其是那些有临床合并症的患者提供了机会。而 PBMC IFN-γ 反应在患有糖尿病的 PTB 中降低。结合 BALF 中的微生物检测，如显微镜和培养，BALMC ELISPOT 为更准确地诊断 PTB，尤其是那些有临床合并症的患者提供了机会。而 PBMC IFN-γ 反应在患有糖尿病的 PTB 中降低。结合 BALF 中的微生物检测，如显微镜和培养，BALMC ELISPOT 为更准确地诊断 PTB，尤其是那些有临床合并症的患者提供了机会。