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Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and

Naomi F Walker1,2,3, Charlotte Schutz1,4, Amy Ward4

  • 1Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Observatory, South Africa.

The Journal of Infectious Diseases
|September 2, 2024
PubMed

Insights

Matrix metalloproteinases (MMPs) are implicated in advanced HIV-TB. Elevated MMP-8 in tuberculosis patients suggests a role in disease progression and mortality, supporting MMP inhibition as a therapeutic strategy.

Area of Science:

  • Immunology
  • Infectious Diseases
  • Biochemistry

Background:

  • High mortality rates in patients with human immunodeficiency virus (HIV)-associated tuberculosis (TB), especially among hospitalized individuals.
  • Understanding the pathophysiological mechanisms of HIV-TB is crucial for developing effective treatments.
  • Matrix metalloproteinases (MMPs) are enzymes involved in tissue remodeling and inflammation, with potential roles in infectious diseases.

Purpose of the Study:

  • To investigate plasma matrix metalloproteinases (MMPs) and matrix-derived biomarkers in hospitalized patients with HIV and TB symptoms.
  • To determine the association of these biomarkers with TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI).
  • To explore the potential of MMP dysregulation in HIV-TB pathophysiology and therapeutic strategies.

Main Methods:

  • Analysis of plasma samples from 433 hospitalized patients with HIV and TB symptoms.
  • Measurement of various MMPs (e.g., MMP-3, -7, -8, -10) and matrix-derived biomarkers (e.g., PIIINP).
  • Correlation of biomarker levels with TB diagnosis, Mtb-BSI, and 12-week mortality.

Main Results:

  • MMP-8 was elevated in patients with confirmed TB and Mtb-BSI compared to other diagnoses.
  • Elevated MMP-8 correlated positively with markers of extracellular matrix breakdown.
  • Baseline levels of MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality.

Conclusions:

  • MMP dysregulation plays a significant role in the pathophysiology of advanced HIV-TB.
  • Specific MMPs are associated with Mtb-BSI and mortality in HIV-infected individuals.
  • MMP inhibition represents a potential host-directed therapeutic strategy for managing HIV-TB.
Keywords:
HIVbiomarkermatrix degradation productmatrix metalloproteinasemortalityprocollagen III N-terminal propeptidetuberculosis

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