Increased level of Serum Adenosine Deaminase (ADA) in blood generally indicates the presence of Tuberculosis
Editors:
- Dr. Praful B. Godkar (Ph.D)
Eminent Author, Medical Biochemist and Scientist, Technical Education consultant. AGD Biomedicals (Pvt) LTD. - Dr. Gauri Kulkarni MD (Pathology)
Vice President, AGD Biomedicals (Pvt) LTD.
Every year more than 9 million new cases of Tuberculosis (TB) are reported worldwide with death rate of around 2 million each year(1). Rapid and accurate diagnosis of TB in population is the most supportive in proper medication and early recovery(8). The golden standard method for diagnosis of tuberculosis in patient is formerly a culture method which is time consuming and cumbersome(8). Various other economical techniques used in the diagnosis of tuberculosis have poor sensitivity and specificity(8). However, serum adenosine deaminase (ADA) has emerged as a potent biochemical marker that can be used as tool for the diagnosis of tuberculosis for rapid, easy and better result(2-5). Increased level of ADA in blood generally indicates the presence of tuberculosis(2). To ensure clinical accuracy and precision in IVD diagnostic ADA test, AGD Biomedicals PVT LTD offers a fifth-generation diagnostic kit fully compliant with stringent global quality management systems, regional regulatory laws, and specific clinical validation guidelines to be legally marketed and used in Clinical laboratories(3).
Q1. Why does serum adenosine deaminase (ADA) rise during TB infection?
ANS(3): An increase in serum adenosine deaminase (ADA) during tuberculosis (TB) infection is fundamentally driven by the body’s cell-mediated immune response. When Mycobacterium tuberculosis enters the body, it triggers a cascade of cellular defense mechanisms that actively synthesize and release this enzyme into the bloodstream
Q2. What is the principle on which serum ADH test is based?
ANS(3,8): Adenosine deaminase hydrolyses adenosine to ammonia & inosine. The ammonia formed further reacts with a phenol as hypochlorite in an alkaline medium to from a blue color indophenol complex with sodium nitroprusside acting as a catalyst. Intensity of the blue colored indophenol complex formed is directly proportional to the amount of ADA present in the sample.
Q3. What is the specificity and sensitivity of serum ADH test of AGD Biomedicals, PVT, LTD. India?
ANS(3): In the diagnosis of pulmonary tuberculosis (PTB), serum adenosine deaminase (ADA) demonstrated the highest diagnostic sensitivity at 88%. This was followed by chest radiography (76%), erythrocyte sedimentation rate (ESR; 72%), sputum acid-fast bacilli (AFB) microscopy (63%), and the Mantoux tuberculin skin test (61%). Serum ADA levels are significantly elevated in patients with PTB compared to those with non-tuberculous pulmonary diseases. Notably, serum ADA levels in sputum AFB-negative PTB cases remain elevated at a magnitude statistically equivalent to sputum AFB-positive cases.
NOTE(1,4-7)
(A) Approximately one-third of the global population is infected with Mycobacterium tuberculosis, putting them at risk of developing active disease. Annually, tuberculosis (TB) affects roughly nine million people and causes 1.5 to 2 million deaths globally. While sputum smear microscopy and culture isolation remain the diagnostic standards, these methods can be difficult to execute. Consequently, rapid alternative diagnostics with acceptable sensitivity and specificity are required for specific clinical scenarios. Although Polymerase Chain Reaction (PCR) is the most sensitive and rapid diagnostic tool, its high-cost limits availability in resource-constrained settings. Alternatively, measuring adenosine deaminase (ADA) enzyme activity in serum and body fluids such as sputum, pleural effusion, ascites, and cerebrospinal fluid presents a viable diagnostic option.
(B) During Treatment Response: If a patient responds well to anti-TB therapy, acute inflammation drops quickly, causing serum CRP levels to plummet early in the treatment cycle. Conversely, cell-mediated immunity remains highly active for a longer period, meaning serum ADA levels can stay elevated for months, even after sputum smear conversion turns negative.
(C) Localized vs. Systemic Disease: In localized extra-pulmonary TB (such as tuberculous pleural effusion or TB meningitis), local ADA levels spike dramatically in the affected fluid. Meanwhile, systemic serum CRP levels may only be mildly or moderately elevated, creating a mismatch between local immune activation and systemic inflammation.
TABLE 1(5): THE ADA-TO-CRP RATIO WITH DIAGNOSTIC PRESENTATION
| CLINICAL CONDITION | ADA/CRP RATIO | DIAGNOSTIC ADVANTAGE |
| Tuberculous Effusion | High: >1.25 | High specific immune response (ADA) paired with moderate general inflammation (CRP). |
| Parapneumonic Effusion (Pneumia) | Low :<0.75 | Massive, acute bacterial inflammation spikes the CRP disproportionately higher than ADA. |
| Malignant Effusion (Cancer) | Low: <0.5 | Moderate tissue inflammation (CRP) without the specific T-cell activation seen in TB. |
NOTE(2-4)
Integrating pleural adenosine deaminase (ADA), cellular ratios, and the serum C-reactive protein (CRP) ratio can yield up to 100% diagnostic sensitivity. Consequently, this combined approach significantly reduces the necessity for invasive tissue biopsies.
References
(1) www.who.int/tb . Global Tuberculosis Control, A short update to the 2009 report.: World health organization (WHO) Library Cataloguing-in-Publication Data; 2009. Available from: http://apps.who. int/iris/bitstream/10665/44241/1/9789241598866_eng.pdf?ua=1.
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(3) Farazi A, Moharamkhani A, Sofian M. Validity of serum adenosine deaminase in diagnosis of tuberculosis. Pan Afr Med J. 2013;15:133.
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(5) Lamsal M, Gautam N, Bhatta N, Majhi S, Baral N, Bhattacharya SK. Diagnostic utility of adenosine deaminase (ADA) activity in pleural fluid and serum of tuberculous and non-tuberculous respiratory disease patients. Southeast Asian J Trop Med Public Health. 2007;38(2):363–9.
(6) Steingart KR, Ng V, Henry M, Hopewell PC, Ramsay A, Cunningham. J, et al. Sputum processing methods to improve the sensitivity of smear microscopy for tuberculosis: a systematic review. Lancet Infect Dis. 2006;6(10):664–74.
(7) Jobayer M, Shamsuzzaman SM, Zulfiquer K. Rapid Diagnosis of Pulmonary Tuberculosis from Sputum by Polymerase Chain Reaction. Arch Clin Infect Dis. 2014;9(2).
(8) Godkar PB, Godkar DP. Textbook of Medical laboratory technology (4th edition, 2024), Bhalani Publishers, Mumbai. India.
