Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium Tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus-Associated Tuberculosis

Overview

Journal J Infect Dis

Publisher Oxford University Press

Specialty Infectious Diseases

Date 2024 Sep 2

PMID 39219411

Authors

Naomi F Walker

Charlotte Schutz

Amy Ward

David Barr

Charles Opondo

Muki Shey

Paul T Elkington

Katalin A Wilkinson

Robert J Wilkinson

Graeme Meintjes

Affiliations

Soon will be listed here.

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.

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