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.
Highlights
Tuberculosis (TB) remains a severe global health problem with 9.0 million new cases and 1.5 million deaths in 2013 [1]
We investigated association between key clinical features of TB documented at time of recruitment and plasma matrix metalloproteinases (MMPs) concentrations by principal component analysis (PCA)
We report the first comprehensive analysis of circulating MMPs including the key comparator group of respiratory symptomatics
Summary
Tuberculosis (TB) remains a severe global health problem with 9.0 million new cases and 1.5 million deaths in 2013 [1]. Analysis of circulating inflammatory mediators in TB, such as cytokines and chemokines, in plasma and serum to define underlying mechanisms of pathogenesis has generally shown surprisingly small differences between patients with TB and control groups [24,25]. These investigations generally do not consider gender differences [24]. We analysed plasma concentrations of MMPs in a prospectively collected cohort of 380 patients with active tuberculosis, healthy controls, and the key comparator group of respiratory symptomatics. MMP-8 concentrations are higher in men than women with TB, highlighting a previously overlooked potential confounder in the investigation of TB pathology and assessment of novel diagnostic strategies
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