Non-specific monocyte activation in MBT blood-based diagnostic tests
Research type
Research Study
Full title
Investigation of non-specific monocyte activation as a cofounder of tuberculosis disease stratification in blood-based diagnostic tests
IRAS ID
360671
Contact name
Marie Voice
Contact email
Sponsor organisation
Birmingham City University
Duration of Study in the UK
0 years, 9 months, 1 days
Research summary
Tuberculosis remains a major global health challenge, with about a quarter of the world’s population infected with Mycobacterium tuberculosis (MTB), and 10–15% developing active disease (WHO, 2025). The QuantiFERON-TB Gold (QFT) blood test is widely used to detect MTB infection. It works by measuring the release of a molecule called interferon gamma (IFN-γ), produced by memory T cells in response to MTB-specific proteins. However, while the QFT test is reliable for identifying infection, it cannot distinguish between latent infection and active TB disease.
Recent studies suggest that other immune cells, particularly monocytes, may contribute to background cytokine production in the QFT assay (Duffy et al., 2021). This non-specific "cytokine noise" may interfere with the true signal from MTB-specific T cells, making it harder to interpret results accurately.
This project aims to measure and better understand the level of non-specific cytokine activity in the QFT test. We will also assess whether blocking monocyte activation using targeted inhibitors such as JTE-607 can reduce background signals without affecting the MTB-specific T cell response. Whole blood from healthy donors will be incubated in QFT tubes with and without the monocyte inhibitor. Cytokine levels will be measured using ELISA, and immune cell activity will be assessed by flow cytometry.
By identifying strategies to minimise non-specific immune activation, this research has the potential to improve the diagnostic accuracy of QFT, particularly in populations where distinguishing between latent and active TB is critical for patient management and ongoing care.References
Duffy D, Rouilly V, Braudeau C, et al; Multinational FOCIS Centers of Excellence. Standardized whole blood stimulation improves immunomonitoring of induced immune responses in multi-center study. Clin Immunol 2017; 183:325–35.
World Health Organization (2024) Tuberculosis. Available at: https://www.who.int/news-room/fact-sheets/detail/tuberculosis (Accessed: 7 July 2025).
REC name
North of Scotland Research Ethics Committee 2
REC reference
25/NS/0089
Date of REC Opinion
20 Jul 2025
REC opinion
Favourable Opinion