Adenosine Deaminase

Adenosine Deaminase (ADA) is an enzyme widely distributed in animal and human tissues. It is found in most cells, but its chief role concerns the proliferation and differentiation of lymphocytes and has been looked on as a marker for cell-mediated hypersensitive reactions. Adenosine Deaminase enzyme is involved in the purine catabolism. It is capable of catalyzing the deamination of adenosine to inosine and of deoxyadenosine to deoxyinosine.

Adenosine Deaminase exists in several isoforms, the prominent ones being ADA1 and ADA2. ADA1 isoenzyme is found in all cells, with the highest concentration in lymphocytes and monocytes, whereas ADA2 isoenzyme appears to be found only in monocytes. ADA2 is the predominant isoform in tuberculous pleural effusion suggesting that ADA2 is the most efficient marker in tuberculosis. However, in clinical practice, the difference in the use of total ADA and isoform ADA2 is not significant.

Increased levels of Adenosine Deaminase have been observed and documented in certain infectious diseases with an active participation of cell-mediated immune responses. Increased serum activity of this enzyme have been found in many infectious diseases caused by microorganisms infecting the macrophages, in leprosy, brucellosis, HIV infections, viral hepatitis, infectious mononucleosis, liver cirrhosis and tuberculosis. Patients with other infectious or non-infectious diseases in which high fever occurred also showed slight to moderate increase in serum Adenosine Deaminase levels.

The diagnosis of pulmonary tuberculosis is confirmed mainly by sputum examination for acid fast bacilli. However, diagnosis of extrapulmonary tuberculosis requires investigation of pleural aspiration, fluid biochemistry, cytology and biopsy. Further, it has been observed that cultures for acid fast bacilli are positive in 20-30% of pleural fluid samples and in 50-80 % of pleural biopsy specimens, making pleural tuberculosis often difficult to diagnose. This is because Mycobacterium tuberculosis in pleural fluid is scanty and rarely observed on direct examination. Relatively new techniques such as Adenosine Deaminase, Interferon Gamma and Polymerase Chain Reaction have been reported to help in diagnosis of tuberculosis. However, the sensitivity of Polymerase Chain Reaction (PCR) for tuberculosis is relatively low (0.42-0.81) and the test is expensive. Interferon Gamma appears to exhibit a better sensitivity (0.89-0.99) but there are relatively few studies of its use. Adenosine Deaminase, has been proposed to be a useful surrogate marker for tuberculosis in pleural, pericardial and peritoneal fluids. Studies have confirmed the high sensitivity and specificity of Adenosine Deaminase for early diagnosis of extrapulmonary tuberculosis and meningitis.  Several studies have suggested that an elevated pleural fluid Adenosine Deaminase level predicts tuberculous pleuritis with a sensitivity of 90-100% and a specificity of 89-100%. The reported cutoff value for Adenosine Deaminase varies from 47 - 60 U/L.

When evaluating Adenosine Deaminase for diagnosis of tuberculosis, an important point to be borne in mind is that levels of Adenosine Deaminase during an infection may vary, due to individual variations in immune response. In the studies, it is well documented that the sensitivity and specificity of Adenosine Deaminase for pleural effusions, pericardial and peritoneal fluids as well as CSF is approximately 90% and thus is strongly recommended for diagnosis of extrapulmonary tuberculosis, in conjunction with other clinical tests.

In case of tuberculous pleurisy, the infection is characterized by the accumulation of activated T- lymphocytes and macrophages in the pleural spaces. The infection being localized and restricted to a certain area result in T-lymphocyte rich pleural effusion, leading to high Adenosine Deaminase concentration in pleural effusions. It was also observed that levels of Adenosine Deaminase in pleural fluid was significantly higher than those observed in serum in both tuberculosis and non-tuberculosis patients, suggesting a localized intrapleural production of Adenosine Deaminase.

Although serum Adenosine Deaminase levels increase during infection with tuberculosis, some researchers suggest that serum Adenosine Deaminase measurement should not be used in tuberculosis for diagnostic purposes. However, it can serve as a useful parameter for the purpose of monitoring therapy provided the base line values before initiation of therapy are determined.

Rapid confirmation of tuberculous meningitis has always been difficult for the microbiologist. Recently, adenosine deaminase, a host enzyme produced by activated T cells and easily detected by a colorimetric procedure, was shown to increase in concentration during the active stage of tuberculous meningitis and to decrease to normal levels after effective antituberculosis therapy.