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Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy

Holmberg, Petter LU ; Janoušková, Martina LU ; Schmidt, Tobias LU ; Neumann, Ariane LU ; Olsson, Oskar LU orcid ; Isberg, Per Erik LU ; Reimann, Maja ; Riesbeck, Kristian LU orcid ; Skogmar, Sten LU and Björkman, Per LU orcid (2025) In Tuberculosis 151.
Abstract

Background: Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT). Methods: Individuals with likelihood of recent Mtb exposure, aged 15–25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included. Persons with TBI were sampled prior to TPT (IGRA + pre-treatment, n = 15) or after completion of TPT (IGRA + post-treatment, n = 15). Five persons without TBI were included as controls (IGRA-). Levels of 40 mediators related to TB immune control in blood incubated... (More)

Background: Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT). Methods: Individuals with likelihood of recent Mtb exposure, aged 15–25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included. Persons with TBI were sampled prior to TPT (IGRA + pre-treatment, n = 15) or after completion of TPT (IGRA + post-treatment, n = 15). Five persons without TBI were included as controls (IGRA-). Levels of 40 mediators related to TB immune control in blood incubated with Mtb antigens in the QuantiFERON-TB Plus® kit were assessed with electrochemiluminescence assay and compared between participant categories. Results: The concentration of 10 mediators (GM-CSF, interferon-γ, IL-2, I-TAC, IL-12, IP-10, I-309, MCP-2, MIG, and VEGF) significantly differed between IGRA + pre-treatment and IGRA-. A non-significant trend in levels of these markers was observed between IGRA + pre-treatment, IGRA + post-treatment and IGRA-. Based on these mediators two clusters were identified: A (n = 16), including 5 IGRA-, 4 IGRA + pre-treatment, 7 IGRA + post-treatment and B (n = 19), including 11 IGRA + pre-treatment and 8 IGRA + post-treatment. Conclusion: Plasma levels of several Mtb-triggered mediators differed with regard to TBI status among persons recently exposed to TB, suggesting the potential for alternative markers to assess TBI status. Longitudinal analysis of these mediators during TPT is warranted to explore whether these markers can be used to assess likelihood of persistence of viable bacilli in Mtb-exposed individuals. ClinicalTrials.govID:NCT05621343.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Tuberculosis
volume
151
article number
102595
publisher
Elsevier
external identifiers
  • scopus:85214201162
  • pmid:39742565
ISSN
1472-9792
DOI
10.1016/j.tube.2024.102595
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2024 The Authors
id
f21138e6-e97c-4503-b6b4-9c62ccdb50ea
date added to LUP
2025-03-14 08:59:58
date last changed
2025-06-06 16:27:50
@article{f21138e6-e97c-4503-b6b4-9c62ccdb50ea,
  abstract     = {{<p>Background: Interferon-γ release assays (IGRAs) for tuberculosis infection (TBI) cannot distinguish different stages of the TBI spectrum (including spontaneously cleared infection). We investigated patterns of Mtb-specific blood mediators in people with and without TBI during tuberculosis preventive therapy (TPT). Methods: Individuals with likelihood of recent Mtb exposure, aged 15–25 years, with valid IGRA results, in whom tuberculosis (TB) had been excluded, were included. Persons with TBI were sampled prior to TPT (IGRA + pre-treatment, n = 15) or after completion of TPT (IGRA + post-treatment, n = 15). Five persons without TBI were included as controls (IGRA-). Levels of 40 mediators related to TB immune control in blood incubated with Mtb antigens in the QuantiFERON-TB Plus® kit were assessed with electrochemiluminescence assay and compared between participant categories. Results: The concentration of 10 mediators (GM-CSF, interferon-γ, IL-2, I-TAC, IL-12, IP-10, I-309, MCP-2, MIG, and VEGF) significantly differed between IGRA + pre-treatment and IGRA-. A non-significant trend in levels of these markers was observed between IGRA + pre-treatment, IGRA + post-treatment and IGRA-. Based on these mediators two clusters were identified: A (n = 16), including 5 IGRA-, 4 IGRA + pre-treatment, 7 IGRA + post-treatment and B (n = 19), including 11 IGRA + pre-treatment and 8 IGRA + post-treatment. Conclusion: Plasma levels of several Mtb-triggered mediators differed with regard to TBI status among persons recently exposed to TB, suggesting the potential for alternative markers to assess TBI status. Longitudinal analysis of these mediators during TPT is warranted to explore whether these markers can be used to assess likelihood of persistence of viable bacilli in Mtb-exposed individuals. ClinicalTrials.govID:NCT05621343.</p>}},
  author       = {{Holmberg, Petter and Janoušková, Martina and Schmidt, Tobias and Neumann, Ariane and Olsson, Oskar and Isberg, Per Erik and Reimann, Maja and Riesbeck, Kristian and Skogmar, Sten and Björkman, Per}},
  issn         = {{1472-9792}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Tuberculosis}},
  title        = {{Blood levels of Mycobacterium tuberculosis (Mtb)antigen-triggered immune markers in people exposed to tuberculosis with regard to Mtb infection status and receipt of tuberculosis preventive therapy}},
  url          = {{http://dx.doi.org/10.1016/j.tube.2024.102595}},
  doi          = {{10.1016/j.tube.2024.102595}},
  volume       = {{151}},
  year         = {{2025}},
}