Dr.Md.Ruhul Amin

Assiatant Registrar

Medicine dept

JRRMCH

Diagnostic value of adenosine deaminase (ADA) activity in tubercular serositis

Introduction: Adenosine deaminase (ADA) is one of

the enzymes in the purine metabolism. It catalyzes the conversion of

adenosine and deoxyadenosine to inosine and deoxyinosine respectively with the release of ammonia.

Importance of ADA: Indicator of active cellular immunity & T

lymphocyte activation. Deficiency of ADA in human manifest

primarily as a severe lymphopenia. Level of ADA increase in tuberculosis

because of stimulation of T cells by mycobacterial antigen.

ADA activity was elevated in the sera from patients with hepatic diseases, hematological malignancies and infectious diseases.

Isoenzyme & Source:

ADA has two principal isoenzymes- i) ADA-1 ii)ADA-2

ADA-1 : Can be found in all cell types. A high ADA1 level indicates cell injury. Serum concentrations of ADA1 were

high in patients with acute leukemias, chronic myeloid leukemia and acute liver injury.

The isoenzyme ADA-1 is elevated in the presence of empyema and parapneumonic effusions.

ADA 2: Found only in macrophage & monocyte. ADA2 comes from stimulated T-cells. Serum ADA2 levels were raised in patients with

tuberculosis adult T-cell leukemia, multiple myeloma infectious mononucleosis , acquired immunodeficiency syndrome,

chronic hepatic diseases

ADA-2 is a more efficient diagnostic marker of TB pleurisy than total ADA activity.

With diagnostic threshold of 40U/L, ADA-2 has 100% sensitivity and 96% specificity for early diagnosis of TB pleurisy.

False positive ADA: False positive results lymphoma, rheumatoid arthritis, SLE adenocarcinoma empyemaIn cases of suspected false negative or

positive ADA levels,level of ADA-1/ ADA(total) ratio is a good parameter.

A proportion of ADA-1/ADA (total) < 0.42 is a good indicator of TB, with an accuracy of 99%, a sensitivity of 100% and a specificity of 98.6% , but high ADA activity with ADA-1/ ADA (total) ratio >0.45 is indicative of malignancy or empyema.

Method of ADA measurement:

Calorometric method of GIUSTI

Plural fluid: Several studies have suggested that an

elevated pleural fluid ADA level predicts tuberculous pleuritis with a sensitivity of 90-100% and a specificity of 89-100% is .The reported cutoff value for ADA (total) varies from 40 to 50 U/L.

One study showed that ADA level, especially when combined with differential cell counts and lymphocyte/neutrophil ratios, remains a useful test in the diagnosis of tuberculous pleuritis.

When the lymphocytes to neutrophils ratio (L/N) > 0.75 was considered together with the ADA activity > 40 U/L, the result improved considerably for the diagnosis of tuberculous pleuritis. The pleural fluid ADA values can be used in conjunciton with cell counts, in the following way: 

1- A lymphocyte exudate (L/N ratio >0.75) with a high ADA value (> 40 U/L) is highly suggestive of TB pleurisy.

2- A lymphocyte exudate with low ADA value (<40 U/L)  is suggestive of nonhematologic malignancies.

3- A neutrophilic exudate (L/N <0.75) with a high ADA concentration (>40 U/L) is suggestive of parainfective effusions.

Pericardial fluid: Using a cutoff value of  ADA activity of

40U/L, the sensitivity and specificity of ADA testing in suspected TB pericarditis were  93%  and  97% respectively . there was a positive correlation between high pericardial adenosine deaminase levels and the subsequent  development of constrictive pericarditis. Therefore, the ADA value is a significant prognostic indicator for the development of constrictive pericarditis in TB pericarditis.

Ascitic fluid: Ascitic fluid ADA activity has been

proposed as a useful diagnostic test for diagnosis of TB peritonitis.

Cutoff level of >30 U/L reported 100% sensitivity for the diagnosis of peritoneal  tuberculosis,  with  specificities  inthe  range  of  92-100%.

False negative results may occur when the ascitic fluid total protein concentration is low as in cirrhosis.

In countries with high incidence of tuberculosis and in high-risk patients, measurement of ADA in ascitic fluid, should be used as a useful screening test for TB but populations with low prevalence of TB & high prevalence of cirrhosis, ascitic fluid ADA activity has good  accuracy but poor sensitivity and imperfect specificity.

CSF:

Cut-off CSF - ADA level of 10 U/L exhibited fairly high accuracy with sensitivity of 94.73%, specificity of 90.47% for the diagnosis of tuberculous meningitis.

Synovial fluid:

The cut-off value for the diagnosis of TB arthritis was SF-ADA 31 U/l, with a sensitivity of 83.3% & specificity of 96.7%

Experience in our center(BSMMU):

Only total ADA done. Cut -off value > 24 U/l for ascitic,plural,

pericardial fluid. > 7 U/L for tubercular meningitis

Sensitivity and specificity Many tests are potentially hazardous and none is completely reliable. All diagnostic tests can produce false positives (an abnormal result in the absence of disease) and false negatives (a normal result in a patient with disease). The diagnostic accuracy of a test can be expressed in terms of its sensitivity and its specificity (Box 1.5).

Sensitivity is defined as the percentage of the test population who are affected by the index condition and test positive for it. In contrast, specificity is defined as the percentage of the test population who are healthy and test negative. A very sensitive test will detect most disease but may generate abnormal findings in healthy people. A negative result will therefore reliably exclude disease but a positive test is likely to require further evaluation. On the other hand, a very specific test may miss significant pathology but is likely to establish the diagnosis, beyond doubt, when the result is positive.