title: Tissue inhibitor of metalloproteinases 1, a novel biomarker of tuberculosis.
abstract: Tuberculosis (TB) is an important infectious disease of humans and other animals. Conventional diagnostic methods, including the tuberculin skin test, chest X‑rays and bacterial culture, have certain innate disadvantages for the early, rapid and specific diagnosis of tuberculosis. The present study aimed to identify a novel diagnostic biomarker to overcome these disadvantages. The potential target identified in the present study was tissue inhibitor of metalloproteinases 1 (TIMP‑1), which has previously been demonstrated to be critical in the immune response to TB. The concentration of TIMP‑1 in the blood was determined using a commercial ELISA kit, and the relative mRNA expression levels following bacterial infection were detected by reverse transcription‑quantitative polymerase chain reaction. Based on a clinical and microbiological diagnosis, the ELISA for plasma TIMP‑1 had a sensitivity of 91.80% [95% confidence interval (CI): 85.44, 96.00] and a specificity of 91.41% (95% CI: 85.14, 95.63). In a THP‑1 cell model, Bacillus Calmette‑Guérin and Mycobacterium bovis significantly upregulated the mRNA expression levels of TIMP‑1 post infection in a time‑dependent manner (P=0.006 for BCG 24 h PI, P=3.2x10‑7 for M. bovis 24 PI). The results of the present study indicate that plasma TIMP‑1 may be a potential biomarker for the diagnosis of TB.
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Yingyu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Pan
authors.initials: P
authors.lastname: Ge
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Dejun
authors.initials: D
authors.lastname: Cao
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Beiping
authors.initials: B
authors.lastname: Miao
authors.affiliation: China Australia Joint Research and Training Center for Veterinary Epidemiology, Wuhan, Hubei 430070, P.R. China.
authors.forename: Ian
authors.initials: I
authors.lastname: Robertson
authors.affiliation: Tuberculosis Department, Wuhan Medical Treatment Center, Wuhan, Hubei 430023, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Tuberculosis Department, Wuhan Medical Treatment Center, Wuhan, Hubei 430023, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Huanchun
authors.initials: H
authors.lastname: Chen
authors.affiliation: The State Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan, Hubei 430070, P.R. China.
authors.forename: Aizhen
authors.initials: A
authors.lastname: Guo
mesh_terms: D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000382:microbiology; D009163:Mycobacterium bovis / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000235:genetics; D014376:Tuberculosis / Q000097:blood* / Q000235:genetics / Q000382:microbiology
chemical_list: D012333:RNA, Messenger; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1