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

Naomi Walker; Charlotte Schutz; Amy Ward; David Barr; Charles Opondo; Muki Shey; Paul T. Elkington; Katalin A. Wilkinson; Robert J. Wilkinson; Graeme Meintjes

doi:10.1093/infdis/jiae296

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

Naomi Walker
, Charlotte Schutz
, Amy Ward
, David Barr
, Charles Opondo
, Muki Shey
, Paul T. Elkington
, Katalin A. Wilkinson
, Robert J. Wilkinson
, Graeme Meintjes

Clinical Sciences

University of Cape Town
London School of Hygiene and Tropical Medicine
University of Liverpool
NHS Greater Glasgow and Clyde
University of Southampton
Mill Hill Laboratory
Imperial College London

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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.

Original language	English
Pages (from-to)	109-114
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	231
Issue number	1
Early online date	2 Sept 2024
DOIs	https://doi.org/10.1093/infdis/jiae296
Publication status	Published - 2 Sept 2024

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

biomarker
HIV
matrix degradation product
matrix metalloproteinase
mortality
procollagen III N-terminal propeptide
tuberculosis

Themes

Tuberculosis and Antimicrobial Resistance

Access to Document

10.1093/infdis/jiae296

Elevated plasma matrix metalloproteinases associate with Mycobaterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosisAccepted author manuscript, 1.69 MB

https://eprints.soton.ac.uk/495004/Licence: CC BY

Cite this

Walker, N., Schutz, C., Ward, A., Barr, D., Opondo, C., Shey, M., Elkington, P. T., Wilkinson, K. A., Wilkinson, R. J., & Meintjes, G. (2024). Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus–Associated Tuberculosis. Journal of Infectious Diseases, 231(1), 109-114. https://doi.org/10.1093/infdis/jiae296

@article{dc8fac3e7c4343acaa1a6a24ff080ed5,

title = "Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus{\textendash}Associated Tuberculosis",

abstract = "Mortality from human immunodeficiency virus (HIV){\textendash}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.",

keywords = "biomarker, HIV, matrix degradation product, matrix metalloproteinase, mortality, procollagen III N-terminal propeptide, tuberculosis",

author = "Naomi Walker and Charlotte Schutz and Amy Ward and David Barr and Charles Opondo and Muki Shey and Elkington, \{Paul T.\} and Wilkinson, \{Katalin A.\} and Wilkinson, \{Robert J.\} and Graeme Meintjes",

year = "2024",

month = sep,

day = "2",

doi = "10.1093/infdis/jiae296",

language = "English",

volume = "231",

pages = "109--114",

journal = "Journal of Infectious Diseases",

issn = "0022-1899",

publisher = "Oxford University Press",

number = "1",

}

Walker, N, Schutz, C, Ward, A, Barr, D, Opondo, C, Shey, M, Elkington, PT, Wilkinson, KA, Wilkinson, RJ & Meintjes, G 2024, 'Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus–Associated Tuberculosis', Journal of Infectious Diseases, vol. 231, no. 1, pp. 109-114. https://doi.org/10.1093/infdis/jiae296

Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus–Associated Tuberculosis. / Walker, Naomi; Schutz, Charlotte; Ward, Amy et al.
In: Journal of Infectious Diseases, Vol. 231, No. 1, 02.09.2024, p. 109-114.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Elevated Plasma Matrix Metalloproteinases Are Associated With Mycobacterium tuberculosis Bloodstream Infection and Mortality in Human Immunodeficiency Virus–Associated Tuberculosis

AU - Walker, Naomi

AU - Schutz, Charlotte

AU - Ward, Amy

AU - Barr, David

AU - Opondo, Charles

AU - Shey, Muki

AU - Elkington, Paul T.

AU - Wilkinson, Katalin A.

AU - Wilkinson, Robert J.

AU - Meintjes, Graeme

PY - 2024/9/2

Y1 - 2024/9/2

N2 - 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.

AB - 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.

KW - biomarker

KW - HIV

KW - matrix degradation product

KW - matrix metalloproteinase

KW - mortality

KW - procollagen III N-terminal propeptide

KW - tuberculosis

U2 - 10.1093/infdis/jiae296

DO - 10.1093/infdis/jiae296

M3 - Article

SN - 0022-1899

VL - 231

SP - 109

EP - 114

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 1

ER -

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

Abstract

UN SDGs

Keywords

Themes

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