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.

Abstract

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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