L-Histidine, arachidonic acid, biliverdin, and L-cysteine-glutathione disulfide as potential biomarkers for cured pulmonary tuberculosis
L-Histidine, arachidonic acid, biliverdin, and L-cysteine-glutathione disulfide as potential biomarkers for cured pulmonary tuberculosis
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L-组氨酸、花生四烯酸、胆绿素和 L-半胱氨酸-谷胱甘肽二硫化物作为治愈肺结核的潜在生物标志物
DOI：
10.1016/j.biopha.2019.108980
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发表时间：
2019
影响因子：
7.5
通讯作者：
Li Ji Cheng
中科院分区：
文献类型：
--
作者：
Yi Wen Jing;Han Yu Shuai;Wei Li Liang;Shi Li Ying;Huang Huai;Jiang Ting Ting;Li Zhi Bin;Chen Jing;Hu Yu Ting;Tu Hui Hui;Li Ji Cheng
缺乏治愈结核病（TB）的实验室标准可能导致未经治疗的结核病患者提前出院，从而增加结核病传播和产生耐药性结核分枝杆菌（Mtb）的风险。我们使用超高效液相色谱-质谱联用（LC-MS）检测未经治疗的结核病患者、治疗2个月的结核病患者、治愈的结核病受试者和健康对照者血浆中的肝素抗凝剂。筛选差异表达的代谢物，结果鉴定出4种差异表达的代谢物，如L-组氨酸、花生四烯酸（AA）、胆绿素和L-半胱氨酸-谷胱甘肽二硫化物。其中l-半胱氨酸-谷胱甘肽二硫化物和AA在TB治疗2个月后可被鉴定。我们建立了治愈的TB模型，曲线下面积（AUC）为0.909（95%CI，0.802-0.970），灵敏度为86.2%，特异性为85.2%。从四种差异代谢物组合（l-组氨酸、AA、胆绿素和l-半胱氨酸-谷胱甘肽二硫化物）拟合的诊断模型可用作治愈TB的潜在生物标志物。本研究为结核病患者出院提供了实验室标准，也为评价抗结核药物疗效提供了实验依据。
Lack of laboratory standards for cured tuberculosis (TB) can lead to early discharge of untreated TB patients from the hospital, resulting in increased risk of TB spread and of developing drug resistantMycobacterium tuberculosis(Mtb). We used ultra-high performance liquid chromatography coupled with mass spectrometry (LC–MS) to detect heparin anticoagulant in plasma of untreated TB patients, two-month treated TB patients, cured TB subjects, and healthy controls. Screening of differentially expressed metabolites resulted in identification of four differentially expressed metabolites such as,l-Histidine, Arachidonic acid (AA), Biliverdin, andl-Cysteine-glutathione disulfide after 6 months of TB treatment. Among them,l-Cysteine-glutathione disulfide and AA could be identified after 2 months of TB treatment. We established a cured TB model with an area under the curve (AUC) of 0.909 (95% CI, 0.802–0.970), 86.2% sensitivity, and 85.2% specificity. The diagnostic model fitted from the four differential metabolites in combination (l-Histidine, AA, Biliverdin, andl-Cysteine-glutathione disulfide) can be used as potential biomarkers for cured TB. Our study provided laboratory standards for hospital discharge of TB patients, as well as experimental basis for evaluating the efficacy of anti-TB drugs.