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.