Interferon-Gamma Release Assays (IGRAs) are blood tests designed to identify tuberculosis (TB) infection. They measure a person’s immune response to the bacteria that cause TB. IGRAs are a significant advancement in diagnostic methods, offering a precise approach to detection and are widely adopted in public health to control TB spread.
Understanding Tuberculosis Infection
Tuberculosis infection occurs when a person harbors Mycobacterium tuberculosis bacteria in their body. It exists in two forms: latent TB infection (LTBI) and active TB disease. In LTBI, the bacteria are inactive, causing no symptoms and not spreading. The immune system contains the germs, preventing illness.
Active TB disease develops when bacteria multiply, leading to symptoms like persistent cough, chest pain, weight loss, fever, and night sweats. Individuals with active TB can transmit the bacteria, especially if the lungs are affected. Detecting LTBI is important because 5-15% of individuals with LTBI will develop active TB disease. Treating LTBI helps prevent this progression, aiding global TB control.
How IGRA Tests Work
IGRA tests measure the immune system’s response to Mycobacterium tuberculosis proteins. When blood from an infected person is exposed to TB antigens in a lab, T cells release interferon-gamma (IFN-γ). This cytokine indicates an immune reaction, and the test quantifies IFN-γ to show past exposure.
Two common IGRA tests are QuantiFERON-TB Gold Plus (QFT-Plus) and T-SPOT.TB. QFT-Plus uses peptides mimicking TB proteins (e.g., ESAT-6, CFP-10) to stimulate T cells. T-SPOT.TB also uses these antigens, measuring IFN-γ producing cells. Both tests detect immune responses to antigens specific to M. tuberculosis, which are largely absent from most non-tuberculous mycobacteria and the BCG vaccine, contributing to their specificity.
Advantages of IGRA Testing
IGRAs offer several advantages over older methods like the tuberculin skin test (TST), also known as the PPD test. IGRAs require only one patient visit for a blood draw, unlike the TST which needs a return visit for interpretation. This simplifies testing and improves compliance.
A significant advantage is that prior Bacillus Calmette-Guérin (BCG) vaccination, which is a vaccine against TB, does not affect IGRA results. TSTs can produce false-positives in BCG-vaccinated individuals, leading to unnecessary follow-up. IGRAs avoid this because they use antigens not present in the BCG vaccine. Furthermore, IGRAs provide objective, quantitative measurements, reducing the subjectivity of TST interpretation.
What Your IGRA Test Results Mean
An IGRA test has specific outcomes. A “positive” result indicates an immune reaction to TB bacteria, suggesting exposure to Mycobacterium tuberculosis. A positive result typically prompts further evaluation, including a chest X-ray and medical history review, to determine if latent TB infection or active TB disease is present.
A “negative” result means no immune reaction to the TB bacteria was observed, suggesting TB infection is unlikely. This outcome usually indicates the individual has not been exposed. However, a negative result does not completely rule out active TB disease, especially in individuals with symptoms or compromised immune systems, requiring clinical judgment and consideration of other factors.
An “indeterminate” or “borderline” result means the test could not provide a clear positive or negative outcome. This can occur due to technical issues with the blood sample, a low immune response, or medical conditions like immunosuppression. In such cases, repeating the IGRA test or considering an alternative method like a TST may be necessary, and further clinical evaluation is recommended.