Can adenosine deaminase activity be measured in serum?

Can ADA Test Be Done on Serum?

Yes, adenosine deaminase (ADA) activity can be measured in serum, but it has limited clinical utility compared to body fluid measurements and should not be used as a primary diagnostic tool for tuberculosis.

Technical Feasibility of Serum ADA Measurement

• Serum ADA can be measured using automated enzymatic methods with acceptable precision (within-assay CV of 5.7% for ADA1 and 2.7% for ADA2) 1
• The test distinguishes between ADA isoenzymes (ADA1 and ADA2), with ADA2 being the predominant form in serum and reflecting monocyte/macrophage activity 2
• Reference intervals for healthy individuals show upper limits of 7.2 U/L for ADA1 and 14.6 U/L for ADA2 1

Clinical Performance in Tuberculosis Diagnosis

Serum ADA in Tuberculous Pleural Effusion

• Mean serum ADA is significantly elevated in tuberculous pleural effusion (34.53 ± 10.27 IU/L) compared to pulmonary TB without effusion (26.54 ± 4.76 IU/L), non-TB respiratory disease (16.71 ± 5.16 IU/L), and healthy controls (15.53 ± 4.4 IU/L) 3
• Using a cutoff of 25 IU/L, serum ADA achieves only 72.41% sensitivity and 81.53% specificity for tuberculous pleural effusion 3

Serum ADA in Pulmonary Tuberculosis

• Serum ADA performs poorly for pulmonary TB diagnosis, with only 35% sensitivity and 91% specificity at a cutoff of 26 IU/L 4
• While specificity is high, the extremely low sensitivity makes serum ADA unsuitable as a diagnostic tool for pulmonary TB 4

Critical Comparison: Serum vs. Body Fluid ADA

Pleural Fluid ADA (Preferred)

• Pleural fluid ADA at a cutoff of 40-45 IU/L achieves 76-90% sensitivity and 77-100% specificity for tuberculous pleurisy 5, 3, 6
• The British Thoracic Society and American College of Chest Physicians recommend pleural fluid ADA measurement, not serum 5, 6

Pericardial Fluid ADA (Preferred)

• Pericardial fluid ADA at a cutoff of 50 IU/L achieves 100% sensitivity and 83% specificity for tuberculous pericarditis 7
• No correlation exists between serum ADA and pericardial fluid ADA levels 7

CSF ADA (Preferred)

• CSF ADA at 9-10 U/L achieves 79% sensitivity and 91% specificity for tuberculous meningitis 6, 8

Clinical Recommendation Algorithm

When to measure ADA:

1. Always measure ADA in the relevant body fluid (pleural, pericardial, peritoneal, or CSF), never rely on serum ADA alone 5, 6, 7
2. If body fluid is available, serum ADA adds no diagnostic value and should not be ordered 7
3. Serum ADA may have limited utility only in resource-restricted settings where body fluid sampling is impossible, but only to rule out disease given its high specificity 4

Critical Pitfalls to Avoid

• Do not use serum ADA as a screening or diagnostic test for tuberculosis - the sensitivity is too low (35%) to be clinically useful 4
• Serum ADA reflects general monocyte/macrophage activity and can be elevated in hepatitis, infectious mononucleosis, pneumonia, and rheumatoid arthritis 2
• Elevated serum ADA in pleural fluid, pericardial fluid, empyema, rheumatoid pleurisy, and malignancy limits its specificity 5, 9
• In HIV-positive patients, ADA levels (both serum and body fluid) may not be elevated even with confirmed tuberculosis 5, 8
• Never delay appropriate body fluid sampling to measure serum ADA instead - this represents suboptimal diagnostic practice 6