1. Academic Validation
  2. 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

  • Biomed Pharmacother. 2019 Aug:116:108980. doi: 10.1016/j.biopha.2019.108980.
Wen-Jing Yi 1 Yu-Shuai Han 2 Li-Liang Wei 3 Li-Ying Shi 4 Huai Huang 5 Ting-Ting Jiang 6 Zhi-Bin Li 7 Jing Chen 8 Yu-Ting Hu 9 Hui-Hui Tu 10 Ji-Cheng Li 11
Affiliations

Affiliations

  • 1 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: 2373052626@qq.com.
  • 2 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: hyshuaizd@zju.edu.cn.
  • 3 Department of Pneumology, Shaoxing Municipal Hospital, Shaoxing, 312000, China. Electronic address: weililiang1981@163.com.
  • 4 Department of Clinical Laboratory, Zhejiang Hospital, Hangzhou, 310058, China. Electronic address: shi-lee-ying@163.com.
  • 5 School of Medicine, South China University of Technology, Guangzhou, 510000, China. Electronic address: yichengshuian5653@163.com.
  • 6 School of Medicine, South China University of Technology, Guangzhou, 510000, China. Electronic address: jiang_tingting1989@126.com.
  • 7 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: lizhibinaa@163.com.
  • 8 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: chenjing2017@zju.edu.cn.
  • 9 School of Medicine, South China University of Technology, Guangzhou, 510000, China. Electronic address: huyuting29@163.com.
  • 10 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: baiweituhuihui@163.com.
  • 11 Institute of Cell Biology, Zhejiang University School of Medicine, Hangzhou, 310058, China. Electronic address: lijichen@zju.edu.cn.
Abstract

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 resistant Mycobacterium 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, and l-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, and l-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.

Keywords

Biomarkers; Metabolomics; Potential cure criteria; Tuberculosis.

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