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.