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Plasma Ribonuclease Activity in Antiretroviral Treatment-Naive People With Human Immunodeficiency Virus and Tuberculosis Disease

Olsson, Oskar LU orcid ; Søkilde, Rolf LU orcid ; Tesfaye, Fregenet LU ; Karlson, Sara LU orcid ; Skogmar, Sten LU ; Jansson, Marianne LU and Björkman, Per LU orcid (2024) In The Journal of infectious diseases 230(2). p.403-410
Abstract

BACKGROUND: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without tuberculosis.

METHODS: Participants were identified from a cohort of treatment-naive PWH in Ethiopia who had been classified for tuberculosis disease (HIV positive [HIV+]/tuberculosis positive [tuberculosis+] or HIV+/tuberculosis negative [tuberculosis-]). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and quantitative polymerase chain reaction and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7, and T2 proteins was performed by... (More)

BACKGROUND: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without tuberculosis.

METHODS: Participants were identified from a cohort of treatment-naive PWH in Ethiopia who had been classified for tuberculosis disease (HIV positive [HIV+]/tuberculosis positive [tuberculosis+] or HIV+/tuberculosis negative [tuberculosis-]). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and quantitative polymerase chain reaction and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7, and T2 proteins was performed by enzyme-linked immunosorbent assay. Ribonuclease activity and protein concentrations were correlated with markers of tuberculosis and HIV disease severity and with concentrations of inflammatory mediators.

RESULTS: Ribonuclease activity was significantly higher in plasma of HIV+/tuberculosis+ (n = 51) compared with HIV+/tuberculosis- (n = 78), causing reduced stability of synthetic spike-in RNAs. Concentrations of ribonucleases 2, 3, and T2 were also significantly increased in HIV+/tuberculosis+ compared with HIV+/tuberculosis-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 cell count, mid-upper arm circumference, and body mass index. Moreover, ribonuclease activity was correlated with concentrations of interleukin 27, procalcitonin and the kynurenine-tryptophan ratio.

CONCLUSIONS: PWH with tuberculosis disease have elevated plasma ribonuclease activity, which is also associated with HIV disease severity and systemic inflammation.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, HIV Infections/blood, Adult, Male, Female, Tuberculosis/blood, Ribonucleases/blood, Ethiopia/epidemiology, Middle Aged, Biomarkers/blood, Cohort Studies, Coinfection/blood, Young Adult
in
The Journal of infectious diseases
volume
230
issue
2
pages
403 - 410
publisher
Oxford University Press
external identifiers
  • scopus:85201701156
  • pmid:38526179
ISSN
1537-6613
DOI
10.1093/infdis/jiae143
language
English
LU publication?
yes
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© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.
id
bae46a8e-490c-4e12-8137-31fbbc03d57e
date added to LUP
2024-09-17 10:46:56
date last changed
2024-10-16 08:38:18
@article{bae46a8e-490c-4e12-8137-31fbbc03d57e,
  abstract     = {{<p>BACKGROUND: The role of ribonucleases in tuberculosis among people with human immunodeficiency virus (HIV; PWH) is unknown. We explored ribonuclease activity in plasma from PWH with and without tuberculosis.</p><p>METHODS: Participants were identified from a cohort of treatment-naive PWH in Ethiopia who had been classified for tuberculosis disease (HIV positive [HIV+]/tuberculosis positive [tuberculosis+] or HIV+/tuberculosis negative [tuberculosis-]). Ribonuclease activity in plasma was investigated by quantification of synthetic spike-in RNAs using sequencing and quantitative polymerase chain reaction and by a specific ribonuclease activity assay. Quantification of ribonuclease 1, 2, 3, 6, 7, and T2 proteins was performed by enzyme-linked immunosorbent assay. Ribonuclease activity and protein concentrations were correlated with markers of tuberculosis and HIV disease severity and with concentrations of inflammatory mediators.</p><p>RESULTS: Ribonuclease activity was significantly higher in plasma of HIV+/tuberculosis+ (n = 51) compared with HIV+/tuberculosis- (n = 78), causing reduced stability of synthetic spike-in RNAs. Concentrations of ribonucleases 2, 3, and T2 were also significantly increased in HIV+/tuberculosis+ compared with HIV+/tuberculosis-. Ribonuclease activity was correlated with HIV viral load, and inversely correlated with CD4 cell count, mid-upper arm circumference, and body mass index. Moreover, ribonuclease activity was correlated with concentrations of interleukin 27, procalcitonin and the kynurenine-tryptophan ratio.</p><p>CONCLUSIONS: PWH with tuberculosis disease have elevated plasma ribonuclease activity, which is also associated with HIV disease severity and systemic inflammation.</p>}},
  author       = {{Olsson, Oskar and Søkilde, Rolf and Tesfaye, Fregenet and Karlson, Sara and Skogmar, Sten and Jansson, Marianne and Björkman, Per}},
  issn         = {{1537-6613}},
  keywords     = {{Humans; HIV Infections/blood; Adult; Male; Female; Tuberculosis/blood; Ribonucleases/blood; Ethiopia/epidemiology; Middle Aged; Biomarkers/blood; Cohort Studies; Coinfection/blood; Young Adult}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{2}},
  pages        = {{403--410}},
  publisher    = {{Oxford University Press}},
  series       = {{The Journal of infectious diseases}},
  title        = {{Plasma Ribonuclease Activity in Antiretroviral Treatment-Naive People With Human Immunodeficiency Virus and Tuberculosis Disease}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiae143}},
  doi          = {{10.1093/infdis/jiae143}},
  volume       = {{230}},
  year         = {{2024}},
}