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Diagnostic Value of Polyfunctional Flow Cytometry Analysis of CD4+ T Cells for Latent Tuberculosis Status
Biomed Sci Letters 2024;30:335-340
Published online December 31, 2024;  https://doi.org/10.15616/BSL.2024.30.4.335
© 2024 The Korean Society For Biomedical Laboratory Sciences.

Jungho Kim1,2,†,*

1Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, Busan 46252, Korea
2Next-Generation Industrial Field-Based Specialist Program for Molecular Diagnostics, Brain Busan 21 Plus Project, Graduate School, Catholic University of Pusan, Busan 46252, Korea
Correspondence to: †Jungho Kim
Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan, 57 Oryundae-ro, Geumjeonggu, Busan 46252, Korea
Tel: +82-51-510-0660, Fax: +82-51-510-0568
E-mail: jutosa70@cup.ac.kr
ORCID: https://orcid.org/0000-0003-3517-2243

*Professor.
Received October 16, 2024; Revised October 23, 2024; Accepted November 8, 2024.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Mycobacterium tuberculosis, the causative agent of tuberculosis (TB), is a major global health concern. Approximately one-third of individuals globally harbors latent TB infection (LTBI), posing a significant challenge as 5%–10% of those infected may develop active TB, especially in individuals with compromised immune systems. Rapid diagnostic tools and targeted LTBI treatments are essential to control TB. This study aimed to investigate the cytokine profiles of CD4+ T cells, particularly polyfunctional CD4+ T cells, as potential diagnostic markers of LTBI. Using a diluted whole-blood intracellular cytokine staining assay, the production of interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and interleukin-2 (IL-2) by CD4+ T cells in 25 participants were measured. The LTBI group exhibited significantly higher frequencies of CD4+ T cells producing IFN-γ, TNF-α, and IL-2 compared to the healthy controls (P = 0.0023, P = 0.0002, P = 0.0473). Polyfunctional CD4+ T cells co-producing IFN-γ, TNF-α, and IL-2 were more prevalent in the LTBI group (P < 0.0001). Receiver operating characteristic curve analysis demonstrated that these cytokine-producing CD4+ T cells are potential biomarkers for LTBI, with polyfunctional CD4+ T cells achieving a sensitivity and specificity of 92.31% and 100.00%, respectively. Polyfunctional CD4+ T cells are potential biomarkers for LTBI diagnosis.
Keywords : Latent tuberculosis infection, T cells, Polyfunctional T cells, Interferon-gamma release assay, Intracellular cytokine staining, Biomarkers