desmosine and Tuberculosis--Pulmonary

Transmission of Mycobacterium tuberculosis (Mtb) continues uninterrupted. Pre-exposure vaccination remains a central focus of tuberculosis research but 25 years of follow up is needed to determine whether a novel childhood vaccination regime protects from adult disease, or like BCG assists Mtb dissemination by preventing childhood illness but not infective adult pulmonary tuberculosis. Therefore, different strategies to interrupt the life cycle of Mtb need to be explored. This personal perspective discusses alternative approaches that may be delivered in a shorter time frame.

Topics: BCG Vaccine; Desmosine; Humans; Lung; Mycobacterium tuberculosis; Tuberculosis, Pulmonary; Vaccination

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.. 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.. 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).. In pulmonary tuberculosis, MMP-driven immunopathology generates matrix degradation products.

Topics: Biomarkers; Coinfection; Desmosine; Extracellular Matrix; HIV Seropositivity; Matrix Metalloproteinases; Peptide Fragments; Procollagen; Reproducibility of Results; ROC Curve; Sputum; Tuberculosis, Pulmonary