adA as a diagnostic tool in tubercular serositis

1. Dr.Md.Ruhul Amin
Assiatant Registrar
Medicine dept
JRRMCH
Diagnostic value of adenosine deaminase
(ADA) activity in tubercular serositis

2.  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.

3. 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.

4. Isoenzyme & Source:
ADA has two principal isoenzymes-
i) ADA-1
ii)ADA-2

5. 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.

6. 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

7.  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.

8. False positive ADA:
 False positive results
lymphoma,
rheumatoid arthritis,
SLE
adenocarcinoma
empyema
In cases of suspected false negative or positive
ADA levels,level of ADA-1/ ADA(total) ratio
is a good parameter.

9.  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.

10. Method of ADA measurement:
 Calorometric method of GIUSTI

11. 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.

12.  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.

13. 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.

14. 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.

15.  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.

16. 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.

17. 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%

18. 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

20. 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