Adenosine deaminase (ADA) is an enzyme in lymphocytes and myeloid cells that recycles toxic purine pathway metabolites, which are essential for DNA metabolism and cell viability. ADA levels are elevated in inflammatory effusions involving pleural, pericardial, and joint fluids due to bacterial infections, granulomatous inflammation, malignancy, and autoimmune diseases. ADA is normally elevated in neutrophil-predominant effusions and is not diagnostically helpful. In lymphocyte-predominant effusions, ADA levels are elevated by tuberculosis (TB) but not by other diseases.
In lymphocyte-predominant effusions, the most common cutoff for ADA is 40 U/L. In a patient with a low pretest probability of tuberculosis and a lymphocyte predominant effusion an ADA level less than or equal to 40 U/L essentially rules out a diagnosis of tuberculosis. An ADA level greater than 40 U/L has a sensitivity of 87% to 93% and specificity of 89% to 97% for tuberculosis. Given a pretest probability of 70% for tuberculosis in a lymphocyte-predominant pericardial effusion in a patient from an endemic country, an ADA level greater than 40 U/L gives a posttest probability of 96%, while a level less than or equal to 40 U/L results in a posttest probability of 19%. An ADA level greater than 40 U/L in a patient with a high pretest probability of disease results in a sufficiently high posttest probability to begin tuberculosis therapy.
False negatives and positive ADA results do occur, so ADA results need to be interpreted along with other laboratory and clinical findings.
References
Chau E, Sarkarati M and Spellberg B. Adenosine deaminase diagnostic testing in pericardial fluid. JAMA published online June 14, 2019. Pages E1-E2.
ArroyoM,SobermanJE.Adenosinedeaminasein the diagnosis of tuberculous pericardial effusion. Am J Med Sci. 2008;335(3):227-229.
Porcel JM, Esquerda A, Bielsa S. Diagnostic performance of adenosine deaminase activity in pleural fluid: a single-center experience with over 2100 consecutive patients. Eur J Intern Med. 2010; 21(5):419-423.