The Quantiferon Gold test is a common diagnostic tool for detecting Tuberculosis (TB) infection. While generally accurate, this blood test can sometimes yield results that don’t align with the actual clinical situation, leading to a “false positive.” Understanding these instances is important for both healthcare providers and individuals undergoing testing. This article explores the test’s mechanisms and reasons for false positives.
What the Quantiferon Gold Test Measures
The Quantiferon Gold (QFT) test is an interferon-gamma (IFN-γ) release assay (IGRA) designed to detect latent TB infection. This blood test works by measuring a person’s immune response to specific proteins from Mycobacterium tuberculosis, the bacterium that causes TB. These proteins, such as ESAT-6, CFP-10, and TB7.7(p4), are absent from most non-tuberculous mycobacteria and all BCG vaccine strains, which helps improve the test’s specificity compared to older methods like the tuberculin skin test (TST).
When a blood sample is collected, it is mixed with these TB-specific antigens and controls in specialized tubes. If an individual has been infected with M. tuberculosis, their white blood cells (specifically T-lymphocytes) will recognize these antigens and release interferon-gamma. The amount of IFN-γ produced is then measured using an enzyme-linked immunosorbent assay (ELISA). A positive result indicates exposure to M. tuberculosis and a cellular immune reaction.
Understanding False Positive Results
A “false positive” QFT result occurs when the test indicates TB infection, but the individual is not actually infected. The false positive rate for the Quantiferon Gold test is estimated to be around 2-3% in some studies. These results can stem from factors including sample handling issues, cross-reactivity with other bacteria, or immune system activations.
Technical or laboratory errors are significant contributors to false positives. Improper blood collection, such as insufficient blood volume, inadequate mixing, or delayed processing, can affect accuracy. Incubation outside the recommended 16 to 24 hours, or improper storage temperatures, can also lead to skewed results. Contamination of the sample with skin microbiota during blood draw can also cause false positive IGRA results.
Cross-reactivity, though less common with QFT than with the PPD skin test, can still occur. Certain non-tuberculous mycobacteria (NTM), such as M. kansasii, M. szulgai, and M. marinum, share antigens with M. tuberculosis and can lead to a positive QFT result. Additionally, immune system activation from other conditions or recent live vaccinations can temporarily influence the test, leading to a false positive. Problems with specific reagent lots, such as faulty TB antigen vials, have also been identified as causes for elevated false positive rates in some cases.
Interpreting and Confirming Results
When a positive Quantiferon Gold result is obtained, healthcare providers undertake a thorough evaluation, especially if a false positive is suspected. Interpretation involves considering the individual’s risk factors for TB exposure. These include travel history to areas where TB is common, close contact with infected individuals, or medical conditions that weaken the immune system, such as HIV infection, diabetes, or immunosuppressive medications.
A positive QFT result does not differentiate between latent TB infection and active TB disease, so further investigation is always necessary. This typically involves a comprehensive clinical assessment, including a review of symptoms, a physical examination, and additional diagnostic tests. A chest X-ray is often performed to check for signs of active disease in the lungs, and sputum cultures may be ordered if active TB is suspected.
In situations where a false positive is suspected, particularly in individuals with low TB exposure risk, healthcare providers might repeat the QFT test or perform another IGRA or a tuberculin skin test (PPD) for comparison. Borderline positive results (e.g., IFN-γ levels between 0.35 and 0.70 IU/mL) in low-prevalence populations are particularly scrutinized and require careful correlation with clinical and epidemiological factors. The goal of this process is to accurately determine if a true infection is present or if the initial positive result was a false positive, ensuring appropriate management and preventing unnecessary treatment.