Sensitive electrochemiluminescence (ECL) immunoassays for detecting lipoarabinomannan (LAM) and ESAT-6 in urine and serum from tuberculosis patients
Sensitive electrochemiluminescence (ECL) immunoassays for detecting lipoarabinomannan (LAM) and ESAT-6 in urine and serum from tuberculosis patients
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DOI：
10.1371/journal.pone.0215443
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发表时间：
2019-04-18
期刊：
影响因子：
3.7
通讯作者：
Sigal, George B.
中科院分区：
文献类型：
--
作者：
Broger, Tobias;Tsionksy, Michael;Sigal, George B.
结核病（TB）感染在2017年估计造成130万人死亡。迫切需要更好的诊断工具。我们试图确定血液或尿液中准确的TB抗原检测是否具有满足WHO用于检测活动性TB的目标产物谱的潜力。材料和方法我们开发了用于脂阿拉伯甘露聚糖（LAM）和ESAT-6检测的电化学发光（ECL）免疫测定，检测限在pg/ml范围内，并使用它们来比较81名HIV感染者的尿液和血清中两种抗原的浓度。结果尿液中LAM和ESAT-6的总敏感性分别为93%和65%。LAM和ESAT-6在血清中的总体敏感性分别为55%和46%。总体特异性为。97%在所有的分析。与HIV阴性患者相比，HIV阳性患者对两种抗原和两种样本类型的敏感性更高，尿液中的信号平均比血清中高约10倍。这两种抗原表现出类似的浓度范围内相同的样品类型和correlated.ConclusionsLAM和ESAT-6可以检测到结核病患者的尿液和血清中，无论艾滋病病毒的状态和临床灵敏度的进一步收益，可以通过检测和试剂优化。尿液中的准确性较高，目前的方法，并有可能达到世界卫生组织的准确性目标，如果发现可以转移到一个床旁结核病测试。
BackgroundTuberculosis (TB) infection was responsible for an estimated 1.3 million deaths in 2017. Better diagnostic tools are urgently needed. We sought to determine whether accurate TB antigen detection in blood or urine has the potential to meet the WHO target product profiles for detection of active TB.Materials and methodsWe developed Electrochemiluminescence (ECL) immunoassays for Lipoarabinomannan (LAM) and ESAT-6 detection with detection limits in the pg/ml range and used them to compare the concentrations of the two antigens in the urine and serum of 81 HIV-negative and -positive individuals with presumptive TB enrolled across diverse geographic sites.ResultsLAM and ESAT-6 overall sensitivities in urine were 93% and 65% respectively. LAM and ESAT-6 overall sensitivities in serum were 55% and 46% respectively. Overall specificity was. 97% in all assays. Sensitivities were higher in HIV-positive compared to HIV-negative patients for both antigens and both sample types, with signals roughly 10-fold higher on average in urine than in serum. The two antigens showed similar concentration ranges within the same sample type and correlated.ConclusionsLAM and ESAT-6 can be detected in the urine and serum of TB patients, regardless of the HIV status and further gains in clinical sensitivity may be achievable through assay and reagent optimization. Accuracy in urine was higher with current methods and has the potential to meet the WHO accuracy target if the findings can be transferred to a point-of-care TB test.