Elevated plasma matrix metalloproteinases associate withMycobacterium tuberculosisblood stream infection and mortality in HIV-associated tuberculosis

Abstract

AbstractMortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality andMycobacterium tuberculosis(Mtb)blood stream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and inMtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP- 3, -7, -8, -10 and procollagen III N-terminal propeptide (PIIINP) associated withMtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV- TB.