Procollagen iii n-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis

Jo Seddon, Victoria Kasprowicz, Naomi F. Walker, Ho Ming Yuen, Henry Sunpath, Liku Tezera, Graeme Meintjes, Robert J. Wilkinson, William R. Bishai, Jon S. Friedland, Paul T. Elkington

Research output: Contribution to journalArticlepeer-review


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 HIVuninfected 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.

Original languageEnglish (US)
Pages (from-to)1571-1578
Number of pages8
JournalJournal of Infectious Diseases
Issue number10
StatePublished - Nov 15 2013
Externally publishedYes


  • Extracellular matrix
  • Immunopathology
  • Lung
  • Matrix metalloproteinase
  • Mycobacteria

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases


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