Tuberculosis (TB) is an infectious disease caused by the bacterium Mycobacterium tuberculosis, which typically affects the lungs but can impact other parts of the body. Historically, detection relied on a skin test with several limitations. The Interferon-Gamma Release Assay (IGRA) is a modern diagnostic advancement, offering a blood test to determine if a person has been infected with TB bacteria. This method measures the body’s specific immune response to the pathogen.
Understanding How IGRA Detects Infection
The IGRA test is founded on the principle of cellular immunity, specifically the response of specialized white blood cells called T-cells. When a person is infected with M. tuberculosis, these T-cells become sensitized to proteins produced by the bacteria. The test works by mixing a patient’s blood sample with synthetic versions of these specific TB-related proteins, which act as antigens.
The antigens used in the test, such as ESAT-6 and CFP-10, are selected because they are present in the TB bacteria but absent from the strains used in the Bacille Calmette-Guérin (BCG) vaccine. If the T-cells in the blood sample have previously encountered the actual TB bacteria, they will recognize these antigens. This recognition triggers an in vitro immune reaction, causing the sensitized T-cells to release a signaling molecule.
This signaling molecule is interferon-gamma (IFN-γ), a cytokine involved in the immune response against intracellular pathogens. The IGRA test quantitatively measures the amount of IFN-γ released into the blood plasma in response to the TB-specific antigens. A high concentration confirms that the person’s immune system has been exposed to and reacted against the M. tuberculosis bacteria.
The measurement of IFN-γ concentration provides an objective, laboratory-based indicator of infection. Different IGRA platforms either measure the IFN-γ concentration or count the number of T-cells actively releasing the cytokine.
The IGRA Testing Process
Undergoing an IGRA test begins with a blood draw performed by a healthcare professional. Unlike older methods, this test requires only a single visit to collect the blood specimen. The blood is collected directly into specialized tubes that contain the TB-specific antigens and control substances.
Following collection, the whole blood sample must maintain the viability of the white blood cells. Depending on the specific IGRA platform used, the sample typically needs to be incubated and analyzed within a strict window, often 8 to 30 hours. This time-sensitive nature ensures the T-cells are active enough to produce a reliable immune response when stimulated in the laboratory.
Once the incubation is complete, results are usually available within 24 to 48 hours of the blood draw. Because the entire reaction takes place in a controlled laboratory setting, the patient does not need to return for a follow-up appointment to have a physical reaction assessed. The single visit and rapid turnaround time have made the IGRA a preferred option in many clinical settings.
Interpreting Your IGRA Results
IGRA results are reported in one of three categories: positive, negative, or indeterminate. A positive result indicates that the person’s blood T-cells released a significant amount of interferon-gamma upon exposure to the TB antigens. This finding strongly suggests that the individual is infected with M. tuberculosis bacteria.
A positive IGRA test indicates a TB infection but cannot distinguish between latent TB infection (LTBI) and active TB disease. Latent infection means the bacteria are present but dormant, causing no symptoms and not transmissible. Active disease means the bacteria are multiplying and causing illness. Therefore, a positive IGRA result requires further medical evaluation, including a chest X-ray, to determine the stage of the infection.
A negative result means that the T-cells did not release sufficient IFN-γ when stimulated by the TB antigens, indicating that infection with M. tuberculosis is unlikely. However, infection cannot be ruled out, especially in individuals who have recently been exposed or who have a weakened immune system that may suppress the T-cell response. In these cases, repeat testing may be recommended.
An indeterminate result occurs when the test controls fail to provide a clear baseline due to an inadequate immune response from the patient or issues with blood sample handling. This outcome is considered inconclusive, meaning the test was unable to determine the presence or absence of infection. An indeterminate result necessitates a repeat IGRA test or consideration of an alternative diagnostic method.
Key Differences From the Traditional Skin Test
The IGRA test offers several advantages over the traditional Tuberculin Skin Test (TST). The most noticeable practical difference is that the IGRA requires only one patient visit for the blood draw, whereas the TST requires a second visit 48 to 72 hours later to measure the skin reaction. This single-visit requirement simplifies the testing process for both patients and clinics.
The objectivity of the results is a key difference, as the IGRA is a quantitative laboratory assay. It measures a specific amount of IFN-γ, providing a numerical result interpreted by machines. The TST, on the other hand, relies on the physical measurement of a raised, hardened area on the skin, a process subject to variation depending on the person performing the assessment.
The IGRA provides a more specific result because it is unaffected by prior BCG vaccination. Many people who received the BCG vaccine test positive with the TST because the TST antigens are similar to those in the vaccine, leading to false-positive results. Since the IGRA uses specific TB antigens absent from the BCG vaccine strain, it is more accurate in vaccinated populations.