Evaluation of cytokines as a biomarker to distinguish active tuberculosis from latent tuberculosis infection: a diagnostic meta-analysis

OBJECTIVES: With a marginally effective vaccine and no significant breakthroughs in new treatments, a sensitive and specific method to distinguish active tuberculosis from latent tuberculosis infection (LTBI) would allow for early diagnosis and limit the spread of the pathogen. The analysis of multiple cytokine profiles provides the possibility to differentiate the two diseases. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Cochrane Library, Clinical Key and EMBASE databases were searched on 31 December 2019. ELIGIBILITY CRITERIA: We included case–control studies, cohort studies and randomised controlled trials considering IFN-γ, TNF-α, IP-10, IL-2, IL-10, IL-12 and VEGF as biomarkers to distinguish active tuberculosis and LTBI. DATA EXTRACTION AND SYNTHESIS: Two students independently extracted data and assessed the risk of bias. Diagnostic OR, sensitivity, specificity, positive and negative likelihood ratios and area under the curve (AUC) together with 95% CI were used to estimate the diagnostic value. RESULTS: Of 1315 records identified, 14 studies were considered eligible. IL-2 had the highest sensitivity (0.84, 95% CI: 0.72 to 0.92), while VEGF had the highest specificity (0.87, 95% CI: 0.73 to 0.94). The highest AUC was observed for VEGF (0.85, 95% CI: 0.81 to 0.88), followed by IFN-γ (0.84, 95% CI: 0.80 to 0.87) and IL-2 (0.84, 95% CI: 0.81 to 0.87). CONCLUSION: Cytokines, such as IL-2, IFN-γ and VEGF, can be utilised as promising biomarkers to distinguish active tuberculosis from LTBI. PROSPERO REGISTRATION NUMBER: CRD42020170725.