Elevated Plasma Matrix Metalloproteinases Are Associated With <i>Mycobacterium tuberculosis</i> Bloodstream Infection and Mortality in Human Immunodeficiency Virus–Associated Tuberculosis
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.
Authors
- Charles Opondo (ORCID: https://orcid.org/0000-0001-8155-4117)
- Graeme Meintjes (ORCID: https://orcid.org/0000-0003-1196-4414)
- Muki Shey (ORCID: https://orcid.org/0000-0002-8776-4737)
- Robert John Wilkinson (ORCID: https://orcid.org/0000-0002-2753-1800)
- Katalin A. Wilkinson (ORCID: https://orcid.org/0000-0002-9796-2040)
- David Barr (ORCID: https://orcid.org/0000-0002-2922-9381)
- Naomi F. Walker (ORCID: https://orcid.org/0000-0002-3345-7694)
- Charlotte Schutz (ORCID: https://orcid.org/0000-0001-8329-6158)
- Paul T. Elkington (ORCID: https://orcid.org/0000-0003-0390-0613)
- Amy Ward (ORCID: https://orcid.org/0000-0002-7725-6763)
Institutions
- University of London (GB)
- University of Liverpool (GB)
- University of Cape Town (ZA)
- Liverpool School of Tropical Medicine (GB)
- The Francis Crick Institute (GB)
- National Institute for Health and Care Research (GB)
- London School of Hygiene & Tropical Medicine (GB)
- Wellcome Trust Liverpool Glasgow Centre for Global Health Research (GB)
- Wellcome Centre for Infectious Diseases Research in Africa (ZA)
- Queen Elizabeth University Hospital (GB)
- University of Southampton (GB)
- Imperial College London (GB)
Publication Details
- Journal
- The Journal of Infectious Diseases
- Published
- 2024-09-02
- DOI
- https://doi.org/10.1093/infdis/jiae296
- Citations
- 4
- Primary Topic
- Pneumocystis jirovecii pneumonia detection and treatment
- Type
- article
- Field-Weighted Citation Impact
- 1.55
Funders
- Wellcome Trust
- Francis Crick Institute
- Imperial Oil Limited
- UK Research and Innovation
- Cancer Research UK
- National Institute for Health and Care Research
- British Heart Foundation
- Diabetes UK
- Imperial College London
- National Research Foundation
- South African Medical Research Council
- British Infection Association
- Mauritius Research Council
- Norsk Revmatikerforbund
- National Institutes of Health
- Medical Research Council
- European and Developing Countries Clinical Trials Partnership