IGRA Tests for Tuberculosis: Blood-Based Diagnostic Tool
Interferon-Gamma Release Assays (IGRAs) are blood tests that detect immune responses to Mycobacterium tuberculosis antigens and are performed on blood samples, not sputum specimens. 1, 2
What is an IGRA Test?
IGRAs are specialized blood tests that measure the immune response to M. tuberculosis antigens by detecting interferon-gamma released by T-cells when exposed to these antigens. The two commercially available IGRAs are:
- QuantiFERON-TB Gold In-Tube (QFT-GIT)
- T-SPOT.TB
Key Characteristics of IGRAs
- Specimen type: Blood sample only (not sputum)
- Mechanism: Measures interferon-gamma released by T-cells in response to M. tuberculosis antigens
- Turnaround time: Results available within 24-48 hours
- Advantages over TST: Not affected by prior BCG vaccination, requires only one patient visit
Diagnostic Significance of a Positive IGRA
A positive IGRA result indicates:
- Immune sensitization to M. tuberculosis antigens
- Probable M. tuberculosis infection (either latent or active)
- Cannot distinguish between latent TB infection (LTBI) and active TB disease 1, 2
Clinical Interpretation and Limitations
- Not a standalone test: Diagnosis should not be based on IGRA results alone but should include epidemiologic history, medical evaluation, and other clinical information 1
- Further evaluation needed: Persons with positive IGRA results should be evaluated for:
- Likelihood of M. tuberculosis infection
- Risk factors for progression to active TB
- Signs and symptoms of active TB disease 1
- Exclusion of active TB: A diagnosis of LTBI requires that active TB be excluded through:
- Medical history and physical examination
- Chest radiography
- Sputum testing when indicated 1
Test Performance
- Sensitivity: T-SPOT.TB (82.3%) has higher sensitivity than QFT-GIT (67.3%) 3
- Specificity: Similar for both tests (T-SPOT.TB: 82.6%, QFT-GIT: 80.4%) 3
- Reduced performance in immunocompromised: Both sensitivity and specificity are lower in HIV-positive patients 4
- Variability: IGRAs can have significant test-to-test variability due to preanalytical, analytical, and immunological factors 5
Clinical Pitfalls and Considerations
- Indeterminate results: May occur, especially in immunocompromised patients (up to 27% in some studies) 6
- Cannot monitor treatment: IGRAs are not reliable for monitoring response to TB treatment as results often remain positive at treatment completion 7
- False positives: More common in low-risk individuals; consider confirmatory testing in low-risk populations 1
- False negatives: Multiple negative results from any combination of tests cannot completely exclude M. tuberculosis infection, especially in immunocompromised patients 1, 2
Testing Strategy Recommendations
- High-risk individuals: Consider dual testing with both TST and IGRA when the risk of infection, progression, and poor outcomes are high 1
- Low-risk individuals: Consider confirmatory testing with a second method when initial test is positive 1
- Indeterminate results: Repeating the IGRA with a new blood sample may provide interpretable results 1
Remember that IGRAs are valuable diagnostic tools for TB infection but must be interpreted in the context of the patient's clinical presentation, risk factors, and additional diagnostic testing.