Association of Serum ADA Levels in Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis

Background: The early diagnosis of pulmonary tuberculosis (PTB) remains a global challenge. While serum adenosine deaminase (ADA) has been associated with tuberculosis-related immune activation, its consistency across different regions and laboratory methods remains unclear. This study aims to evaluate group-level differences in serum ADA levels and identify factors influencing these variations. Methods: A systematic search was conducted across PubMed, Embase, and Scopus up to February 2026. A meta-analysis using a random-effects model was performed to calculate the pooled standardized mean difference (SMD), reflecting group-level differences in serum ADA levels between PTB patients and control groups. Results: Thirty-four studies were included. Serum ADA levels were significantly higher in PTB patients compared to healthy controls (SMD = 3.15, 95% CI: [2.51-3.79], p < 0.0001) and other respiratory diseases (SMD = 2.06, 95% CI: [1.38-2.74], p < 0.0001). Subgroup analyses revealed that geographical region and ADA measurement methods did not significantly account for the observed high heterogeneity (I² > 95%), indicating that ADA elevation was consistently observed across studies. Conclusions: Serum ADA levels were significantly elevated in patients with PTB, indicating a consistent biological association with disease status. However, given the high heterogeneity and the absence of diagnostic accuracy measures (e.g., sensitivity and specificity), these findings should not be interpreted as evidence of clinical diagnostic performance. Further diagnostic test accuracy studies are required to establish its clinical utility.