A Comprehensive Meta-Analytical Evidence on IFN-γ and TNF-α as Diagnostic and Treatment Monitoring Biomarkers in Tuberculosis
Keywords:
Tuberculosis, Interferon-gamma, Tumor Necrosis Factor-alpha, Biological Markers, Diagnosis, Treatment, Monitoring, Systematic ReviewAbstract
Background: The accurate diagnosis and effective surveillance of tuberculosis (TB) is a global health issue. The responsible cytokines in host immune response against Mycobacterium tuberculosis were interferon-gamma (IFN-γ) and tumor necrosis factor -alpha (TNF-α). This study was aimed at synthesizing the existing evidence on diagnostic accuracy of IFN-γ and TNF-α levels in TB, and to evaluate their role in monitoring treatment response. Methods: This review followed PRISMA 2020 guidelines for its synthesis. Relevant published articles from in PubMed, Scopus, Web of Science, and Google Scholar from 2016 to 2025 were analyzed. The included studies were those that compared circulating IFN-γ and/or TNF-α levels in patients with TB, with or without treatment. Review-based studies, and studies without comparable biomarker data were excluded. For risk of bias assessment, Newcastle-Ottawa Scale was utilized, and the certainty of evidence was measured through GRADE framework. Results: The analysis of 12 included studies demonstrated that high levels of IFN-γ were a uniform biomarker of diagnosis for latent and active TB infection, whereas higher levels of TNF-α level were associated with active pulmonary TB. Longitudinal data showed that reduction in both cytokine levels was associated with successful treatment outcomes, while their persistent elevated levels suggested poor outcomes or relapse. Risk of bias among studies was low to moderate, and certainty of evidence was found to be moderate. Conclusion: IFN-γ was a good diagnostic biomarker throughout the TB spectrum, TNF-α was promising in the detection of active disease and assessment of therapeutic response.
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