Elevated plasma matrix metalloproteinases are associated with Mycobacterium tuberculosis bloodstream infection and mortality in human immunodeficiency virus-associated tuberculosis

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Naomi F Walker Charlotte Schutz Amy Ward David Barr Charles Opondo Muki Shey Paul T Elkington Katalin Wilkinson Robert Wilkinson Graeme Meintjes
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Abstract

Mortality from human immunodeficiency virus (HIV)-associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-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.

Journal details

Journal Journal of Infectious Diseases
Volume 231
Issue number 1
Pages 109-114
Available online
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Publisher website (DOI) 10.1093/infdis/jiae296
Download Download full text [pdf]
Europe PubMed Central 39219411
Pubmed 39219411

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The publication was previously a preprint. View preprint