Use of pleural fluid levels of adenosine deaminase and interferon gamma in the diagnosis of tuberculous pleuritis

PURPOSE OF REVIEW: This review aims to define the role of adenosine deaminase (ADA) and interferon gamma (IFN-gamma) in the differential diagnosis of pleural effusion with special attention to their source, mechanism of release and methods of measurement in pleural fluid. The diagnostic performance of ADA and IFN-gamma is analyzed, and the advantages and limitations of their use in differentiating between tuberculous and nontuberculous pleural effusion are discussed. RECENT FINDINGS: Several potential biomarkers of tuberculous pleurisy have been evaluated, but none have been found to be clearly superior to pleural fluid level of ADA or IFN-gamma. The majority of recent studies confirm the high diagnostic utility of pleural fluid ADA and IFN-gamma measurement; hence, these markers are included in different diagnostic algorithms for patients suspected of tuberculous pleurisy. Other relatively new tests show a high variability [nucleic acid amplification tests (NAATs)] or are technically demanding, costly and give equivocal results in patients with active tuberculosis [IFN-gamma releasing assays (IGRAs)]. SUMMARY: Pleural fluid ADA and IFN-gamma are both sensitive and specific biomarkers of tuberculous pleurisy. Their diagnostic accuracy across the different studies shows a smaller variability than that of other tests, for example NAATs. There is also no convincing evidence that IGRAs are superior to pleural fluid ADA or IFN-gamma measurement. Hence, the role of ADA and IFN-gamma in the differential diagnosis of tuberculous pleurisy is pivotal.