Infection and Drug Resistance (Aug 2022)

A Peptidomic Approach to Identify Novel Antigen Biomarkers for the Diagnosis of Tuberculosis

  • Chen H,
  • Li S,
  • Zhao W,
  • Deng J,
  • Yan Z,
  • Zhang T,
  • Wen SA,
  • Guo H,
  • Li L,
  • Yuan J,
  • Zhang H,
  • Ma L,
  • Zheng J,
  • Gao M,
  • Pang Y

Journal volume & issue
Vol. Volume 15
pp. 4617 – 4626

Abstract

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Hongmei Chen,1,* Shanshan Li,2,* Weijie Zhao,3,* Jiaheng Deng,4,* Zhuohong Yan,5 Tingting Zhang,2 Shu’ an Wen,2 Haiping Guo,2 Lei Li,6 Jianfeng Yuan,6 Hongtao Zhang,5 Liping Ma,1 Jianhua Zheng,4,* Mengqiu Gao,1 Yu Pang2 1Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 2Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Clinical Trial Agency Office, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 4Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, and Center for Tuberculosis Research, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Central Laboratory, Beijing Chest Hospital, Capital Medical University/Beijing Tuberculosis & Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 6Electral Safety Research & Development Center, Beijing Normal University, Zhuhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yu Pang, Department of Bacteriology and Immunology, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10 8950 9359, Email [email protected] Mengqiu Gao, Department of Tuberculosis, Beijing Chest Hospital, Capital Medical University/ Beijing Tuberculosis & Thoracic Tumor Research Institute, No. 9, Beiguan Street, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 10 8950 9302, Email [email protected]: Here, we conducted a peptidomic study in murine model to identify novel antigen biomarkers for the diagnosis of tuberculosis (TB) with improved performance.Methods: Four recombinant proteins, including Mycobacterium tuberculosis protein 32 (MPT32), Mycobacterium tuberculosis protein 64 (MPT64), culture filtrate protein 10 (CFP10), and phosphate ABC transporter substrate-binding lipoprotein (PstS1) were expressed and intravenously injected into BALB/c mice. The serum were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The concentrations of candidate peptides in serum of suspected TB patients were determined using competitive enzyme-linked immunosorbent assay.Results: A total of 65 peptides from 4 MTB precursor recombinant proteins were identified in mouse serum by LC-MS/MS, of which 5 peptides were selected as candidates for serological analysis. The concentrations of peptides MPT64-2, CFP10-2 and PstS1-2 in TB patients were significantly higher than those in non-TB patients. MPT64-2 exhibited the most promising sensitivity (81.4%), followed by PstS1-2 and CFP10-2. In addition, PstS1-2 had the highest specificity (93.3%), followed by CFP10-2 and MPT64-2. According to the area under the curve (AUC), MPT64-2 (AUC = 0.863), PstS1-2 (AUC = 0.812) and CFP10-2 (AUC = 0.809) exhibited better diagnostic validity.Conclusion: We develop an effective approach to identify new antigen biomarkers via LC-MS/MS-based peptidomics. Multiple peptides exhibit promising efficacy in diagnosis of active TB patients.Keywords: tuberculosis, peptidomics, enzyme-linked immunosorbent assay, Mycobacterium tuberculosis protein 64, diagnostics

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