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 - 2025/1/15
Y1 - 2025/1/15
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 -
