Interferon-Gamma Release Assay (IGRA) Test
An Interferon-Gamma Release Assay (IGRA) is a blood test that detects Mycobacterium tuberculosis infection by measuring the release of interferon-gamma from T cells in response to M. tuberculosis-specific antigens. 1 These tests serve as an important alternative to the traditional tuberculin skin test (TST) for diagnosing latent tuberculosis infection.
How IGRAs Work
IGRAs function by detecting the cellular immune response to specific M. tuberculosis antigens:
- They measure interferon-gamma (IFN-γ) released by sensitized T cells when exposed to highly specific M. tuberculosis antigens 2
- The antigens used include:
- Early secretory antigen (ESAT-6)
- Culture filtrate protein (CFP-10)
- TB7.7 (in some assays)
- These antigens are encoded by genes in the RD-1 gene segment, which is present in M. tuberculosis but absent from BCG vaccine strains and most non-tuberculous mycobacteria 2
Types of FDA-Approved IGRAs
There are two main commercially available IGRAs:
QuantiFERON-TB Gold In-Tube (QFT-GIT):
- Whole blood is drawn into heparinized tubes coated with antigens
- After 16-24 hours of incubation, IFN-γ concentration is measured by ELISA
- Includes nil control and mitogen control tubes 2
T-SPOT.TB:
- Uses the ELISPOT method
- Measures the number of T cells producing IFN-γ 2
Advantages of IGRAs Over TST
- Higher specificity in BCG-vaccinated individuals (prevents false positives common with TST) 1
- No need for a return visit - results available within 24 hours 1
- Eliminates subjective interpretation as they are laboratory-based assays 1
- No boosting effect - unlike TST, repeat testing doesn't boost subsequent results 1
- Preferred in populations with low rates of return for TST reading (e.g., homeless persons, drug users) 1
Limitations of IGRAs
- Can have indeterminate results, particularly in immunocompromised patients 1
- Limited data on predictive value for progression to active TB 1
- Higher cost than TST, though potentially offset by reduced false positives and elimination of return visits 1
- May cross-react with certain non-tuberculous mycobacteria (M. kansasii, M. szulgai, M. marinum) due to RD1 homology 3, 4
Testing Protocol Requirements
- Tests must be performed according to FDA-approved protocols 1
- Laboratory must comply with Clinical Laboratory Improvement Amendment (CLIA) standards 1
- Blood collection must be arranged prior to specimen collection to ensure proper handling 1
- Both qualitative interpretation and quantitative measurements should be reported 1
Clinical Applications
- Diagnosis of latent tuberculosis infection
- Aid in diagnosing active tuberculosis (though not sufficient alone)
- Particularly useful in:
- BCG-vaccinated individuals
- Healthcare workers
- Immunocompromised patients (though interpretation may be more difficult)
- Contact investigations 2
IGRAs represent a significant advancement in tuberculosis diagnostics, offering improved specificity over the traditional TST, especially in BCG-vaccinated populations, while maintaining comparable sensitivity for detecting M. tuberculosis infection.