Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis

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Background.Tuberculosis (TB) is transmitted by patients with pulmonary disease. Matrix metalloproteinases (MMPs) drive lung destruction in TB 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 HIV positive and negative patients with pulmonary TB and controls. Concentrations of MDPs and MMPs were analyzed by ELISA and Luminex array in two patient cohorts.Results.Procollagen III N-terminal propeptide (PIIINP) was 3.8-fold higher in induced sputum of HIV-uninfected TB patients compared to controls and desmosine, released during elastin degradation, was 2.4-fold higher. PIIINP was elevated in plasma of TB 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<0.001). Plasma matrix metalloproteinase-8 concentrations were also higher in TB patients (p=0.001). Receiver operating characteristic analysis utilising these two variables demonstrated an area under the curve of 0.832 (p <0.001).Conclusions.In pulmonary TB, MMP-driven immunopathology generates matrix degradation products.

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Volume 208
Issue number 10
Pages 1571-1579
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