Mycobacterium tuberculosis-specific cytokine biomarkers to differentiate active TB and LTBI: A systematic review

• Published in: The Journal of infection 2020-12, Vol.81 (6), p.873-881
• Main Authors: Sudbury, Eva L., Clifford, Vanessa, Messina, Nicole L., Song, Rinn, Curtis, Nigel
• Format: Article
• Language: English
• Subjects: Active TB; Adult; Antigens, Bacterial; Biomarkers; Child; Cytokine biomarkers; Cytokines; Humans; Latent Tuberculosis - diagnosis; LTBI; Mycobacterium tuberculosis; Systematic review; Tuberculosis; Tuberculosis - diagnosis
• ISSN: 0163-4453; 1532-2742
• DOI: 10.1016/j.jinf.2020.09.032

•Current diagnostic tests do not discriminate active TB from latent TB infection.•Several novel cytokines show promise as stage-specific markers of TB infection.•Inconsistent results across studies likely resulted from heterogeneous study design.•Combinations of cytokines may perform better than any single cytokine alone.•Further well-designed studies are needed for development of next generation tests. New tests are needed to overcome the limitations of existing immunodiagnostic tests for tuberculosis (TB) infection, including their inability to differentiate between active TB and latent TB infection (LTBI). This review aimed to identify the most promising cytokine biomarkers for use as stage-specific markers of TB infection. A systematic review was done using electronic databases to identify studies that have investigated Mycobacterium tuberculosis (MTB)-specific cytokine responses as diagnostic tools to differentiate between LTBI and active TB. The 56 studies included in this systematic review measured the MTB-specific responses of 100 cytokines, the most frequently studied of which were IFN-γ, IL-2, TNF-α, IP-10, IL-10 and IL-13. Ten studies assessed combinations of cytokines, most commonly IL-2 and IFN-γ. For most cytokines, findings were heterogenous between studies. The variation in results likely relates to differences in the study design and laboratory methods, as well as participant and environmental factors. Although several cytokines show promise as stage-specific markers of TB infection, this review highlights the need for further well-designed studies, in both adult and paediatric populations, to establish which cytokine(s) will be of most use in a new generation of immunodiagnostic tests.