Adenosine Deaminase (ADA) is an enzyme found throughout the body. The ADA assay is a common laboratory test designed to measure the activity level of this enzyme in a fluid sample. Quantifying the amount of ADA present helps medical professionals gain insight into specific disease processes and immune system function.
The Role of Adenosine Deaminase in the Body
The primary function of the ADA enzyme is its involvement in the purine metabolism pathway. ADA catalyzes the irreversible conversion of adenosine and deoxyadenosine into inosine and deoxyinosine, a step necessary to clear these nucleosides from the body.
ADA is present in nearly all human tissues, but its highest concentrations are found within lymphoid tissues, such as the thymus and spleen. The enzyme protects immune cells, especially lymphocytes (T-cells and B-cells), from the toxic effects of accumulating high levels of deoxyadenosine. If the enzyme is absent or non-functional, the buildup of these molecules severely impairs immune cell development and survival.
ADA Assay for Tuberculosis Diagnosis
The most frequent clinical use of the ADA assay is diagnosing extrapulmonary tuberculosis (EPTB), an infection occurring outside of the lungs. When the body mounts an immune response against Mycobacterium tuberculosis, T-lymphocytes migrate to the infection site and dramatically increase their production of the ADA enzyme.
Measuring ADA activity in the fluid surrounding the infected organ (serosal fluid) serves as a reliable marker for EPTB. High ADA levels in pleural fluid suggest tuberculous pleurisy, while high levels in cerebrospinal fluid (CSF) may indicate tuberculous meningitis. This test is fast, less expensive, and highly useful where advanced diagnostic technologies are unavailable. An ADA level greater than 40 International Units per liter (IU/L) in pleural fluid is frequently used as a strong indicator of the disease.
ADA Assay for SCID Screening and Diagnosis
The ADA assay is also utilized in the diagnosis of Adenosine Deaminase Deficiency Severe Combined Immunodeficiency (ADA-SCID), a rare, inherited genetic condition. This disorder is caused by a mutation in the gene, leading to a profound deficiency or complete absence of ADA activity. The lack of functional ADA allows toxic metabolites to accumulate, destroying developing T-cells and B-cells.
Infants with untreated ADA-SCID have a severely compromised immune system, making them susceptible to recurrent, life-threatening infections. Because of the severity of the disease and the positive outcomes associated with early intervention, ADA-SCID is increasingly included in newborn screening (NBS) programs. Testing aims to identify infants before symptoms appear, allowing for prompt treatment such as enzyme replacement or gene therapy. The assay looks for an abnormally low or absent level of ADA activity in the infant’s blood or dried blood spot sample.
Performing and Interpreting ADA Assay Results
The ADA assay is an enzymatic test that measures the rate at which the enzyme converts its substrate into a product over a set period. The sample type depends on the suspected condition; blood is used for systemic issues like SCID, while serosal fluids, such as peritoneal, pleural, or cerebrospinal fluid, are collected for suspected EPTB. The resulting enzyme activity is quantified in units per liter (U/L) or international units per liter (IU/L).
Interpretation of the results relies on comparing the measured activity level to established reference ranges specific to the fluid type and the patient’s age.
Interpreting High ADA Levels
An elevated or high ADA level in a serosal fluid, such as pleural fluid, typically points toward an infection that has triggered a significant T-lymphocyte response, most commonly extrapulmonary tuberculosis. For instance, a result above 40 IU/L in pleural fluid is a strong diagnostic indicator.
Interpreting Low ADA Levels
Conversely, an absent or severely low ADA level, particularly in a blood sample from an infant, strongly suggests the genetic disorder ADA-SCID. This finding indicates the body cannot clear toxic purine metabolites, leading to immune cell destruction. A normal ADA result generally suggests that the enzyme is functioning correctly within the fluid tested and that a diagnosis of EPTB or ADA-SCID is unlikely.