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[Preprint]. 2023 Dec 13:2023.12.12.23299845.
doi: 10.1101/2023.12.12.23299845.

Elevated plasma matrix metalloproteinases associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosis

N F Walker  1   2   3 , C Schutz  2   4 , A Ward  4 , D Barr  2   5   6 , C Opondo  7 , M Shey  2   4 , P T Elkington  8 , K A Wilkinson  2   4   9 , R J Wilkinson  2   4   9   10 , G Meintjes  2   4
Affiliations

Elevated plasma matrix metalloproteinases associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated tuberculosis

N F Walker et al. medRxiv. .

Update in

Abstract

Mortality from HIV-associated tuberculosis (HIV-TB) is high, particularly among hospitalised patients. In 433 people living with HIV admitted to hospital with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality and Mycobacterium tuberculosis (Mtb) blood stream 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 procollagen III N-terminal propeptide (PIIINP) 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: HIV; Tuberculosis; matrix metalloproteinase; mortality.

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Conflict of interest statement

Conflicts of Interest All authors: No conflicts of interest to declare.

Figures

Figure 1
Figure 1. Elevated matrix metalloproteinase-8 in HIV-TB, Mtb-blood stream infection and TB mortality Plasma matrix metalloproteinase (MMP)-8
(A) and Col4α1 (B) were elevated in hospitalised participants with HIV infection and microbiologically-confirmed TB, compared to hospitalised HIV positive participants with symptoms due to other diagnoses (no TB). Differences between patients with confirmed TB and TB diagnosed clinically were not statistically significant. Plasma MMP-8 was increased in participants with confirmed TB and Mycobacterium tuberculosis blood stream infection (MTBBSI) compared to those without (C) and in those who had died compared to those who had survived at 12 weeks (D). Col4α1 was measured in a subset of 73 participants. *p<0.05, **p<0.01, ***p<0.001.
Figure 2
Figure 2. Plasma matrix metalloproteinase (MMP) and procollagen III N-terminal propeptide (PIIINP) associate with Mycobacterium tuberculosis blood stream infection and mortality in HIV-associated TB.
A and B: Analyte (log concentration, x-axes) associations (y-axes) with Mycobacterium tuberculosis blood stream infection (MTBBSI) and mortality. Odds ratios (OR) and p-values are from logistic regression models, with adjustment for random effects by plate. C: Log neutrophil and procalcitonin (x-axes) associations (y-axes) with MTBBSI and mortality. All panels: Loess fit to data is shown (coloured lines with shaded 95% confidence intervals).
See this image and copyright information in PMC

References

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