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

Petter Holmberg; Martina Janoušková; Tobias Schmidt; Ariane Neumann; Oskar Olsson; Per-Erik Isberg; Maja Reimann; Kristian Riesbeck; Sten Skogmar; Per Björkman

doi:10.1016/j.tube.2024.102595

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

Tuberculosis (Edinb). 2024 Dec 20:151:102595. doi: 10.1016/j.tube.2024.102595. Online ahead of print.

Authors

Affiliations

¹ Clinical Infection Medicine, Department of Translational Medicine, Lund University, Ruth Lundskogs gata 3, SE214 28, Malmö, Sweden. Electronic address: [email protected].
² Clinical Microbiology, Department of Translational Medicine, Faculty of Medicine, Lund University, Inga Marie Nilssons gata 53, SE-214 28, Malmö, Sweden.
³ Department of Clinical Sciences Lund, Division of Pediatrics, Lund University, 221 84, Lund, Sweden.
⁴ Department of Clinical Sciences Lund, Division of Infection Medicine, Lund University, BMC I12, 221 84, Lund, Sweden.
⁵ Clinical Infection Medicine, Department of Translational Medicine, Lund University, Ruth Lundskogs gata 3, SE214 28, Malmö, Sweden.
⁶ Department of Statistics, Lund University, Box 7080, 220 07, Lund, Sweden.
⁷ Division of Clinical Infectious Diseases, Research Center Borstel, Parkallee 1-40, 23845, Borstel, Germany; German Center for Infection Research (DZIF) Partner Site Hamburg-Lübeck-Borstel-Riems, Borstel, Germany; Respiratory Medicine and International Health, University of Lübeck, Ratzeburger Allee, 16023562, Lübeck, Germany.

PMID: 39742565
DOI: 10.1016/j.tube.2024.102595

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 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.

Associated data

ClinicalTrials.gov/NCT05621343