A tuberculosis (TB) blood test, also known as an Interferon-Gamma Release Assay (IGRA), determines if an individual has been infected with Mycobacterium tuberculosis, the bacteria that causes TB. These tests detect the body’s immune response to these bacteria. A positive result suggests the presence of TB, indicating a past or current infection. This can signify either active disease or a latent, inactive infection. Understanding these test results, including the possibility of false positives, is important for accurate diagnosis and management.
How TB Blood Tests Work
TB blood tests, or Interferon-Gamma Release Assays (IGRAs), measure the immune system’s response to proteins unique to tuberculosis bacteria. When infected with Mycobacterium tuberculosis, white blood cells (T-lymphocytes) develop a memory of these proteins. If re-exposed to these TB-specific proteins in a test tube, these sensitized T-cells release interferon-gamma (IFN-γ).
The two main FDA-approved IGRA tests, QuantiFERON-TB Gold Plus and T-SPOT.TB, quantify this IFN-γ response. QuantiFERON-TB Gold Plus measures IFN-γ concentration, while T-SPOT.TB counts IFN-γ-producing cells. IGRAs are generally more specific than the older tuberculin skin test (TST), especially for individuals who have received the Bacille Calmette-Guérin (BCG) vaccine. The antigens used in IGRAs are largely absent from the BCG vaccine, reducing false positives from vaccination.
Understanding Positive Test Results
A positive TB blood test result typically signifies infection with Mycobacterium tuberculosis. This often indicates latent TB infection (LTBI), where TB bacteria are present but inactive. Individuals with LTBI do not experience symptoms, are not sick, and cannot spread the bacteria. A positive IGRA result for LTBI is a true positive for infection, even without active disease.
The immune system usually contains latent bacteria, preventing illness. Without treatment, latent TB can progress to active TB disease, where bacteria multiply, cause symptoms, and become transmissible. A positive IGRA result prompts further evaluation, such as a chest X-ray and symptom assessment, to differentiate between latent infection and active disease.
A “true false positive” result occurs when the test indicates TB infection, but no Mycobacterium tuberculosis bacteria are actually present. These occurrences are less common with IGRAs than skin tests due to the specific antigens used. However, certain factors can still lead to these misleading results, requiring careful consideration by healthcare providers.
Specific Reasons for False Positive Results
Exposure to certain non-tuberculous mycobacteria (NTM) can cause false positive IGRA results. Environmental mycobacteria, common in soil and water, sometimes share antigens similar to Mycobacterium tuberculosis. This can trigger a weak cross-reaction, where the immune system reacts to similar proteins even without actual TB bacteria. While IGRAs are highly specific, some NTM species can induce a low-level immune response misinterpreted as TB infection.
Laboratory or handling errors can also contribute to false positive TB blood tests. Improper blood sample collection, processing delays, or incorrect storage temperatures can affect white blood cell viability. Errors during laboratory analysis, such as contamination or misinterpretation, though rare in accredited labs, can also lead to erroneous positive outcomes. Adherence to strict protocols minimizes these errors.
Recent BCG vaccination has limited impact on IGRA results compared to tuberculin skin tests. While BCG can cause false positives with skin tests, IGRAs use antigens largely absent from the BCG vaccine. Therefore, a false positive due to BCG vaccination is uncommon with IGRA tests unless administered very recently (within the last year or two).
Other rare factors may influence IGRA results. Certain medical conditions affecting the immune system or specific medications, like immunosuppressants, could theoretically impact test accuracy. However, such instances are infrequent, and their precise influence on false positive rates is still being researched. Environmental mycobacteria exposure and issues with sample handling or laboratory procedures remain the primary causes for a true false positive.
Next Steps After a Positive Test
Receiving a positive TB blood test result necessitates immediate consultation with a healthcare provider. The physician will assess individual risk factors, including TB exposure, recent travel to high-prevalence areas, and any symptoms of active TB disease. This clinical evaluation helps determine the likelihood of true infection versus a potential false positive.
Further diagnostic testing is a standard next step to clarify the positive result. A chest X-ray is commonly performed to check for signs of active TB in the lungs. If symptoms like persistent cough, fever, or weight loss are present, sputum tests may be ordered to directly look for Mycobacterium tuberculosis. These additional tests help differentiate between latent infection, active disease, or a false positive.
Based on the comprehensive assessment and additional test results, the healthcare provider will determine the appropriate course of action. If latent TB infection is confirmed, antibiotic treatment is often recommended to prevent progression to active disease. If active TB disease is suspected, more extensive treatment and isolation measures may be initiated. If a false positive is strongly suspected, retesting or continued monitoring might be advised.