The QuantiFERON-TB Gold (QFT-G) test is a blood test specifically designed to identify latent tuberculosis infection (LTBI), caused by the bacterium Mycobacterium tuberculosis. While this test typically provides clear positive or negative results, an “indeterminate” outcome can occur.
The QuantiFERON-TB Gold Test
The QuantiFERON-TB Gold test is an interferon-gamma release assay (IGRA) that serves as a modern alternative to the traditional tuberculin skin test (TST) for diagnosing latent tuberculosis infection. It works by measuring the immune system’s response to specific proteins found in Mycobacterium tuberculosis. When blood from an infected individual is exposed to these TB-specific antigens, their T-cells release interferon-gamma (IFN-γ).
The QFT-G test utilizes four blood collection tubes: a negative control, a positive control (mitogen), and two tubes containing TB-specific antigens (TB1 and TB2). The amount of IFN-γ produced in each tube is then measured. A “positive” result indicates that the individual’s immune system has reacted to the TB antigens, suggesting a likely M. tuberculosis infection. Conversely, a “negative” result implies no significant immune response to the TB antigens, indicating that infection is unlikely.
Understanding an Indeterminate Result
An “indeterminate” QuantiFERON-TB Gold test result signifies that the test could not provide a definitive positive or negative interpretation. This outcome does not confirm or rule out the presence of M. tuberculosis infection. Instead, it indicates an inconclusive technical result, often linked to the quality of the blood sample or the patient’s immune response. This means the laboratory was unable to obtain a clear reading, highlighting that the assay did not function as expected to yield a conclusive measurement of interferon-gamma.
Common Reasons for Indeterminate Results
Indeterminate QFT-G results can stem from biological factors related to the patient’s immune system and technical issues during sample collection or laboratory processing. A weakened immune system is a common biological contributor.
Patients who are immunocompromised due to conditions like HIV, chronic renal disease, autoimmune diseases, or those receiving immunosuppressive medications, may exhibit a reduced or absent immune response. This can lead to a low response in the mitogen (positive control) tube, which signals that the patient’s T-cells were unable to produce sufficient interferon-gamma even when stimulated with a general immune activator. Elderly individuals, especially those over 65, and patients with conditions like low lymphocyte or albumin levels are also more likely to have indeterminate results.
Technical and procedural factors can also lead to indeterminate results. Improper blood sample collection or handling is a frequent cause. This includes incorrect filling or mixing of the specialized QuantiFERON tubes, insufficient sample volume (each tube requires 1 mL of blood), or delayed processing, particularly if the sample is not incubated within 16 hours of collection. Storage at incorrect temperatures, such as refrigeration, can also affect cell viability and impact the test’s accuracy. High background levels of interferon-gamma in the negative control tube can also make the result uninterpretable.
Next Steps After an Indeterminate Result
When an indeterminate QuantiFERON-TB Gold result is obtained, medical professionals typically initiate a comprehensive evaluation. A thorough clinical assessment considers the patient’s symptoms, medical history, and any known risk factors for tuberculosis exposure to guide subsequent decisions.
Repeating the QFT-G test is often the immediate next step, allowing for a fresh sample and careful adherence to collection and handling protocols to address potential technical issues. If the repeat QFT-G test also yields an indeterminate result or if clinical suspicion for TB remains high, alternative diagnostic methods may be pursued. These can include another type of interferon-gamma release assay or the tuberculin skin test (TST). Further diagnostic procedures, such as a chest X-ray or sputum cultures, are considered if active tuberculosis disease is suspected, and these investigations should not be delayed. For individuals with persistent indeterminate results, particularly those who are immunocompromised, consultation with an infectious disease specialist may be recommended.