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Plasma profiles of inflammatory markers associated with active tuberculosis in antiretroviral therapy-naive human immunodeficiency virus-positive individuals

Olsson, Oskar LU ; Björkman, Per LU ; Jansson, Marianne LU ; Balcha, Taye Tolera LU ; Mulleta, Daba; Yeba, Habtamu; Valfridsson, Christine LU ; Carlsson, Fredric LU and Skogmar, Sten LU (2019) In Open Forum Infectious Diseases 6(2).
Abstract

Background. Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals. Methods. Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type... (More)

Background. Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals. Methods. Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels. Results. The HIV+/TB+ subjects had higher levels of all markers, except IL12p70, compared with HIV+/TB subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV+/TB+ and HIV+/TB, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count <200 cells/mm3]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts. Conclusions. Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarker, CRP, HIV, Mycobacterium tuberculosis, Sub-Saharan Africa
in
Open Forum Infectious Diseases
volume
6
issue
2
publisher
Oxford University Press
external identifiers
  • scopus:85066460906
ISSN
2328-8957
DOI
10.1093/ofid/ofz015
language
English
LU publication?
yes
id
aae8a5ed-f7bc-4c3c-aad1-e97ecb67c22b
date added to LUP
2019-06-17 19:27:09
date last changed
2019-07-09 04:48:23
@article{aae8a5ed-f7bc-4c3c-aad1-e97ecb67c22b,
  abstract     = {<p>Background. Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals. Methods. Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV<sup>+</sup>/TB<sup>+</sup>) and 130 subjects without TB (HIV<sup>+</sup>/TB<sup>−</sup>) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels. Results. The HIV<sup>+</sup>/TB<sup>+</sup> subjects had higher levels of all markers, except IL12p70, compared with HIV<sup>+</sup>/TB<sup>−</sup> subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV<sup>+</sup>/TB<sup>+</sup> and HIV<sup>+</sup>/TB<sup>−</sup>, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count &lt;200 cells/mm<sup>3</sup>]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts. Conclusions. Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.</p>},
  articleno    = {ofz015},
  author       = {Olsson, Oskar and Björkman, Per and Jansson, Marianne and Balcha, Taye Tolera and Mulleta, Daba and Yeba, Habtamu and Valfridsson, Christine and Carlsson, Fredric and Skogmar, Sten},
  issn         = {2328-8957},
  keyword      = {Biomarker,CRP,HIV,Mycobacterium tuberculosis,Sub-Saharan Africa},
  language     = {eng},
  month        = {02},
  number       = {2},
  publisher    = {Oxford University Press},
  series       = {Open Forum Infectious Diseases},
  title        = {Plasma profiles of inflammatory markers associated with active tuberculosis in antiretroviral therapy-naive human immunodeficiency virus-positive individuals},
  url          = {http://dx.doi.org/10.1093/ofid/ofz015},
  volume       = {6},
  year         = {2019},
}