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PLoS One. 2015 Jan 30;10(1):e0117605. doi: 10.1371/journal.pone.0117605. eCollection 2015.

Gender-dependent differences in plasma matrix metalloproteinase-8 elevated in pulmonary tuberculosis.

Author information

1
Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
2
NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
3
The Royal London Hospital, Whitechapel, United Kingdom.
4
NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
5
Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom.
6
Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; Microbiology, Universidad Cayetano Heredia, Lima, Peru.
7
Infectious Diseases and Immunity, Imperial College London, London, United Kingdom; NIHR Southampton Respiratory Biomedical Research Unit, Clinical and Experimental Sciences Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom; Institute for Life Sciences, University of Southampton, Southampton, United Kingdom.

Abstract

Tuberculosis (TB) remains a global health pandemic and greater understanding of underlying pathogenesis is required to develop novel therapeutic and diagnostic approaches. Matrix metalloproteinases (MMPs) are emerging as key effectors of tissue destruction in TB but have not been comprehensively studied in plasma, nor have gender differences been investigated. We measured the plasma concentrations of MMPs in a carefully characterised, prospectively recruited clinical cohort of 380 individuals. The collagenases, MMP-1 and MMP-8, were elevated in plasma of patients with pulmonary TB relative to healthy controls, and MMP-7 (matrilysin) and MMP-9 (gelatinase B) were also increased. MMP-8 was TB-specific (p<0.001), not being elevated in symptomatic controls (symptoms suspicious of TB but active disease excluded). Plasma MMP-8 concentrations inversely correlated with body mass index. Plasma MMP-8 concentration was 1.51-fold higher in males than females with TB (p<0.05) and this difference was not due to greater disease severity in men. Gender-specific analysis of MMPs demonstrated consistent increase in MMP-1 and -8 in TB, but MMP-8 was a better discriminator for TB in men. Plasma collagenases are elevated in pulmonary TB and differ between men and women. Gender must be considered in investigation of TB immunopathology and development of novel diagnostic markers.

PMID:
25635689
PMCID:
PMC4312016
DOI:
10.1371/journal.pone.0117605
[Indexed for MEDLINE]
Free PMC Article

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