The Adenosine Deaminase (ADA) test measures the ADA enzyme level in bodily fluids, most commonly pleural fluid, to aid in diagnosing tuberculosis (TB) in the pleura—the membranes surrounding the lungs. Elevated ADA levels are often linked to TB in this region. This blog explores the ADA test, its normal range, significance, and more.

What is Adenosine Deaminase (ADA)?

Adenosine Deaminase (ADA) is an enzyme crucial for purine metabolism in the body. Its primary role is to break down adenosine from food, facilitating the turnover of nucleic acids across various tissues. The ADA test is primarily used to assess and support the development and maintenance of the immune system. Additionally, ADA plays minor but significant roles in functions such as gestation maintenance, amino acid release, neurotransmission, and epithelial cell differentiation.

What is an ADA Test?

The Adenosine Deaminase (ADA) test is conducted to measure ADA levels in pleural fluid and is primarily used to diagnose Mycobacterium tuberculosis, commonly known as tuberculosis (TB). In rare cases, it may also be used to evaluate other infections.

What is ADA normal range?

The ADA normal range in both males and females, regardless of their age, is less than 40 Units/L. A normal Adenosine Deaminase level does not mean that one is not suspected of tuberculosis or other infections. TB may have normal ADA levels in some cases, which can be confirmed after specific diagnostic tests.

If ADA levels are found to be higher than 40 Units/L, it might indicate certain diseases such as:

• Pneumonia associated with TB
• Tubercular ascites
• Lymphadenitis of TB
• Pleural TB
• Synovitis caused by rheumatoid arthritis
• Meningitis of TB

1. Higher ADA Levels and Their Clinical Implications

Elevated levels of ADA indicate a number of conditions, such as tuberculosis and malignant lymphoma. Other diseases that can cause high ADA levels include:

• Malignant pleural effusion
• Sarcoidosis
• Pulmonary embolism
• Autoimmune diseases
• Parapneumonic effusion

Increased serum ADA activity can be seen in diseases associated with cellular system stimulation which are as follows: 

• Typhoid fever
• Liver disease
• Sarcoidosis
• Infectious mononucleosis
• Leukaemia
• Acute pneumonia
• Malignancies
• Rheumatoid arthritis
• Tuberculosis

2. Low ADA Levels and its Clinical Implications

ADA deficiency affects the development and function of immune cells called lymphocytes. These are white blood cells that help the body fight infections. People with low levels of ADA often develop chronic diarrhoea, pneumonia and widespread skin rashes.

ADA deficiency leads to the build-up of toxic by-products and can cause severe combined immunodeficiency disease (SCID). It indicates a number of conditions, including:

• Tuberculous pleurisy: Low activity of ADA in pleural fluid can be a sign of atypical tuberculosis in patients who are critically ill, elderly or have multi-organ failure.
• Immunodeficiency: A rare inherited condition that impairs the development and function of lymphocytes, white blood cells that help the body fight infections.
• Other diseases: Low ADA levels in pleural fluid can also indicate other diseases.

Why Should One Take the ADA Test?

The doctor recommends an ADA test to identify or rule out the disease Mycobacterium tuberculosis in patients. The test helps detect TB in one’s pleural fluid and thereby helps in its diagnosis. Under rare circumstances, the test is used to identify different infections in other fluids, such as the cerebrospinal fluid (CSF) or the peritoneal fluid.

In some cases, doctors recommend the ADA test to patients to rule out the possibilities of TB, under the following circumstances:

• Pregnancy
• People with a very low immune system
• Children who are positive in a TB screening test
• People who migrated from areas where the occurrence of TB was very high
• People who work in hospitals, social workers or others who have been in close contact with patients with TB for a long time

Conditions Affecting ADA Levels

One of the primary factors affecting Adenosine Deaminase (ADA) levels is genetic mutations in the ADA gene. This can lead to a deficiency in the enzyme, causing a condition known as “Adenosine Deaminase Deficiency.” This is a severe combined immunodeficiency (SCID) where the body is unable to properly break down adenosine, leading to a build-up of toxic metabolites and impaired immune function.

Hence, factors that affect ADA levels include:

• Immune cell impact
• Mutation severity
• Genetic mutations

To a lesser extent, other potential factors that may influence ADA levels include certain cancers, tissue sampling location and inflammatory conditions.

Purpose of the ADA Test

The primary purpose of the ADA test is to evaluate the level of ADA enzyme in the blood. It is conducted for the following:

• Diagnosing tuberculosis, where TB infection involves the pleura or the central nervous system
• Identifying lymphocytic pleural effusion among those infected
• Identifying meningitis

ADA Test Procedure and Methods

An ADA test collects a sample of pleural fluid from the chest cavity through a procedure called thoracentesis. In this procedure, a healthcare professional inserts a needle to extract the fluid, which is analysed in a lab to measure the Adenosine Deaminase level. The ADA test is primarily used as an indicator for potential TB infection in the pleural space. It is often used in conjunction with other diagnostic methods like AFB smear and culture. The ADA test procedure includes patient preparation, sample collection (thoracentesis), and sample processing.

There are two methods for measuring ADA activity and they are as follows:

• Spectrophotometric method: This measures the absorbance of light at a specific wavelength to determine the amount of ADA present.
• Colorimetric method: This is the most common method for measuring ADA activity. It uses a chemical reaction in which the enzyme ADA converts adenosine into inosine, producing ammonia, which is later detected by a colour change.

Interpretation of ADA Test Results

Elevated ADA levels in pleural fluid suggest the presence of tuberculosis; however, further investigations are important for a definitive diagnosis. Lower ADA levels indicate a decreased likelihood of tuberculosis. Therefore, low ADA levels can virtually rule out a diagnosis of TB with a lymphocytic pleural effusion.

If initial ADA levels are higher, follow-up tests may include repeating the ADA test to monitor treatment response. Other follow-up tests may include acid-fast bacillus smear and culture, pleural fluid analysis or molecular tuberculosis testing.

Understanding False Positives and Negatives

A false positive in an ADA test means that the test result indicates tuberculosis presence when the patient doesn’t have it, while a false negative means the test shows the absence of TB, but the patient is infected. This usually occurs due to factors like low levels of TB bacteria, recent infection, and other conditions that elevate ADA levels, such as inflammatory diseases or certain cancers.

Causes of false positives of the ADA test can include sample contamination, high cut-off value or other inflammatory conditions.

Conclusion

The ADA test is essential in diagnosing tuberculosis, particularly in pleural effusions and other diseases. Elevated ADA levels can indicate immune system activity, which helps to identify infections and inflammatory conditions. The ADA test is important to support accurate diagnosis and timely treatment, ensuring better health management.