Procollagen III N-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis.
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.
Infectious Diseases and Immunity.
Jo
J
Seddon
Victoria
V
Kasprowicz
Naomi F
NF
Walker
Ho Ming
HM
Yuen
Henry
H
Sunpath
Liku
L
Tezera
Graeme
G
Meintjes
Robert J
RJ
Wilkinson
William R
WR
Bishai
Jon S
JS
Friedland
Paul T
PT
Elkington
D015415:Biomarkers; D060085:Coinfection; D003895:Desmosine / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D006679:HIV Seropositivity; D020782:Matrix Metalloproteinases / Q000097:blood / Q000378:metabolism*; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism*; D011347:Procollagen / Q000097:blood / Q000378:metabolism*; D012372:ROC Curve; D015203:Reproducibility of Results; D013183:Sputum / Q000737:chemistry; D014397:Tuberculosis, Pulmonary / Q000378:metabolism* / Q000473:pathology*
D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D003895:Desmosine; D020782:Matrix Metalloproteinases
extracellular matrix; immunopathology; lung; matrix metalloproteinase; mycobacteria