Centre for Vaccines & Immunology, National Institute of Communicable Diseases, A Division of the National Health Laboratory Service, Johannesburg, South Africa; Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Department of Chemical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.
Int J Infect Dis. 2020 Oct;99:441-448. doi: 10.1016/j.ijid.2020.08.028. Epub 2020 Aug 12.
The World Health Organization has identified the need for a non-sputum-based test capable of detecting active tuberculosis (TB) as a priority. The plasma kynurenine-to-tryptophan (K/T) ratio, largely mediated by activity of the enzyme indoleamine 2,3-dioxygenase, may have potential as a suitable biomarker for active TB.
We evaluated a commercial enzyme-linked immunosorbent assay (ELISA) in comparison to mass spectrometry for measuring the K/T ratio. We also used ELISA to determine the K/T ratio in plasma from patients with active TB compared to latently infected controls, with and without HIV.
The two methods showed good agreement, with a mean bias of 0.01 (limit of agreement from -0.06 to 0.10). Using ELISA, it was found that HIV-infected patients with active TB disease had higher K/T ratios than those without TB (median, 0.101 [interquartile range (IQR), 0.091-0.140] versus 0.061 [IQR, 0.034-0.077], P<0.0001). At a cutoff of 0.080, the K/T ratio produced a sensitivity of 90%, a specificity of 80%, a positive predictive value (PPV) of 82%, and a negative predictive value (NPV) of 90%. In a receiver operating characteristics analysis, the K/T ratio had an area under the curve of 0.93. HIV-uninfected patients with active TB also had higher K/T ratios than those with latent TB infections (median, 0.064 [IQR, 0.040-0.088] versus 0.022 [IQR, 0.016-0.027], P<0.0001). A cutoff of 0.040 gave a sensitivity of 85%, a specificity of 92%, a PPV of 91%, and an NPV of 84%.
The plasma K/T ratio is a sensitive biomarker for active TB. The K/T ratio can be measured from blood using ELISA. The K/T ratio should be evaluated as an initial test for TB.
世界卫生组织已经确定需要一种基于非痰液的检测方法来检测活动性结核病（TB），这是一项优先事项。血浆犬尿氨酸与色氨酸（K/T）比值主要由酶吲哚胺 2,3-双加氧酶的活性介导，可能具有作为活动性 TB 合适的生物标志物的潜力。
我们评估了一种商业酶联免疫吸附测定（ELISA）与质谱法测量 K/T 比值的比较。我们还使用 ELISA 测定了 HIV 感染者中活动性 TB 患者与潜伏性感染对照者的血浆 K/T 比值，包括有和没有 HIV 的患者。
两种方法具有良好的一致性，平均偏差为 0.01（界限从 -0.06 到 0.10）。使用 ELISA，我们发现 HIV 感染的活动性 TB 患者的 K/T 比值高于无 TB 的患者（中位数，0.101[四分位距（IQR），0.091-0.140]比 0.061[IQR，0.034-0.077]，P<0.0001）。在 0.080 的截止值下，K/T 比值的灵敏度为 90%，特异性为 80%，阳性预测值（PPV）为 82%，阴性预测值（NPV）为 90%。在受试者工作特征分析中，K/T 比值的曲线下面积为 0.93。HIV 未感染的活动性 TB 患者的 K/T 比值也高于潜伏性 TB 感染的患者（中位数，0.064[IQR，0.040-0.088]比 0.022[IQR，0.016-0.027]，P<0.0001）。0.040 的截止值具有 85%的灵敏度、92%的特异性、91%的阳性预测值和 84%的阴性预测值。
血浆 K/T 比值是活动性 TB 的敏感生物标志物。K/T 比值可以使用 ELISA 从血液中测量。K/T 比值应作为 TB 的初始检测进行评估。
