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Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis
Jo Seddon1, Victoria Kasprowicz, Naomi F Walker
1Infectious Diseases and Immunity.
Background:
Tuberculosis is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in tuberculosis but the resulting matrix degradation products (MDPs) have not been studied. We investigate the hypothesis that MMP activity generates matrix turnover products as correlates of lung pathology.
Methods:
Induced sputum and plasma were collected prospectively from human immunodeficiency virus (HIV) positive and negative patients with pulmonary tuberculosis and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in 2 patient cohorts.
Results:
Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected tuberculosis patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of tuberculosis patients. Plasma PIIINP correlated with induced sputum MMP-1 concentrations and radiological scores, demonstrating that circulating MDPs reflect lung destruction. In a second patient cohort of mixed HIV seroprevalence, plasma PIIINP concentration was increased 3.0-fold above controls (P < .001). Plasma matrix metalloproteinase-8 concentrations were also higher in tuberculosis patients (P = .001). Receiver operating characteristic analysis utilizing these 2 variables demonstrated an area under the curve of 0.832 (P < .001).
Conclusions:
In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.
Insights
Matrix metalloproteinases (MMPs) generate matrix degradation products (MDPs) in tuberculosis lung disease. These circulating MDPs, like procollagen III N-terminal propeptide (PIIINP), correlate with lung pathology and can help diagnose tuberculosis.
Area of Science:
- Pulmonary Medicine
- Immunopathology
- Biochemistry
Background:
- Tuberculosis (TB) transmission occurs via pulmonary disease patients.
- Matrix metalloproteinases (MMPs) are implicated in lung destruction during TB.
- Matrix degradation products (MDPs) resulting from MMP activity in TB have not been well-studied.
Purpose of the Study:
- To investigate if MMP activity generates matrix turnover products (MDPs) that correlate with lung pathology in tuberculosis.
- To assess the diagnostic potential of MDPs and MMPs in pulmonary tuberculosis.
Main Methods:
- Prospective collection of induced sputum and plasma from HIV-positive and negative pulmonary TB patients and controls.
- Analysis of MDPs and MMP concentrations using ELISA and Luminex array in two distinct patient cohorts.
Main Results:
- Procollagen III N-terminal propeptide (PIIINP) and desmosine were significantly elevated in the sputum of HIV-uninfected TB patients.
- Plasma PIIINP levels correlated with sputum MMP-1 and radiological scores, indicating reflection of lung destruction.
- Plasma PIIINP and MMP-8 concentrations were higher in TB patients, achieving an AUC of 0.832 for diagnosis.
Conclusions:
- Matrix metalloproteinase-driven immunopathology in pulmonary tuberculosis generates measurable matrix degradation products.
- Circulating MDPs, particularly PIIINP, serve as valuable biomarkers for lung destruction in TB.
- Combined analysis of PIIINP and MMP-8 shows promise for diagnosing pulmonary tuberculosis.
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