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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Procollagen iii n-terminal propeptide and desmosine are released by matrix destruction in pulmonary tuberculosis
Journal of Infectious Diseases, Volume 208, No. 10, Year 2013
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Description
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. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3805234/bin/supp_208_10_1571__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3805234/bin/supp_jit343_jit343supp.pdf
Authors & Co-Authors
Seddon, Jo
United Kingdom
Infectious Diseases and Immunity
United Kingdom, London
Imperial College London
Kasprowicz, Victoria O.
South Africa, Durban
The Nelson R. Mandela Medical School
United States, Cambridge
Massachusetts Institute of Technology
Walker, Naomi F.
United Kingdom
Infectious Diseases and Immunity
United Kingdom, London
Imperial College London
South Africa, Cape Town
University of Cape Town
Yuen, Ho Ming
United Kingdom, Southampton
University of Southampton, Faculty of Medicine
Sunpath, Henry
South Africa, Durban
Mccord Hospital
South Africa, Durban
The Nelson R. Mandela Medical School
Tezera, Liku B.
United Kingdom, Southampton
University of Southampton, Faculty of Medicine
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
Meintjes, Graeme Ayton
South Africa, Cape Town
University of Cape Town
United Kingdom, London
Imperial College London
Wilkinson, Robert J.
United Kingdom
Infectious Diseases and Immunity
United Kingdom, London
Imperial College London
United Kingdom, London
Mrc National Institute for Medical Research
Bishai, William R.
South Africa, Durban
The Nelson R. Mandela Medical School
Friedland, Jon S.
United Kingdom
Infectious Diseases and Immunity
United Kingdom, London
Imperial College London
Elkington, Paul
United Kingdom
Infectious Diseases and Immunity
United Kingdom, Southampton
University of Southampton, Faculty of Medicine
United Kingdom, Southampton
University Hospital Southampton Nhs Foundation Trust
United Kingdom, Southampton
University of Southampton
Statistics
Citations: 41
Authors: 11
Affiliations: 10
Identifiers
Doi:
10.1093/infdis/jit343
ISSN:
00221899
Research Areas
Health System And Policy
Infectious Diseases
Study Design
Cohort Study