What is the Interferon-Gamma Release Assay (IGRA) test?

Interferon-Gamma Release Assay (IGRA) Test

The 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

How IGRAs Work

IGRAs detect sensitization to M. tuberculosis by measuring interferon-gamma (IFN-γ) release when a patient's blood is exposed to antigens specific to M. tuberculosis. These tests are based on the principle that T cells previously exposed to M. tuberculosis will rapidly release IFN-γ when re-exposed to mycobacterial antigens.

Types of FDA-Approved IGRAs

1. QuantiFERON-TB Gold In-Tube test (QFT-GIT) - Manufactured by Cellestis Limited
2. T-SPOT.TB test (T-Spot) - Manufactured by Oxford Immunotec Limited
3. QuantiFERON-TB Gold test (QFT-G) - An earlier version

Advantages of IGRAs over Tuberculin Skin Test (TST)

• Higher specificity - IGRAs use M. tuberculosis-specific antigens (ESAT-6, CFP-10, TB 7.7) that are absent from BCG vaccine strains and most non-tuberculous mycobacteria 1, 2
• Single patient visit - Results available within 24 hours without requiring a return visit
• No reader bias - Laboratory-based assays eliminate subjective interpretation
• No boosting effect - Unlike TST, IGRAs do not boost subsequent test results 1

Clinical Applications

IGRAs are used as aids in:

• Diagnosing M. tuberculosis infection (both latent infection and active tuberculosis)
• Surveillance for tuberculosis infection
• Identifying persons who would benefit from treatment for latent tuberculosis infection (LTBI)

Preferred Use Scenarios

IGRAs are preferred over TST in:

• BCG-vaccinated individuals - Prevents false positives common with TST in this population 1
• Populations with low rates of return for TST reading - Such as homeless persons and drug users 1
• Cost-effective screening of high-risk populations, particularly BCG-vaccinated immigrants 3

Limitations

• Indeterminate results - Can occur, particularly in immunocompromised patients
• Limited data on predictive value for progression to active TB
• Logistical challenges - Requires proper blood collection, handling, and processing within specific timeframes 4
• Higher cost than TST, though potentially offset by reduced false positives 1
• Possible cross-reactivity with certain non-tuberculous mycobacteria like M. kansasii, M. marinum, and M. szulgai 5

Test Selection Considerations

When choosing between TST and IGRA, consider:

• Patient population characteristics
• Prior BCG vaccination status
• Likelihood of return for TST reading
• Test availability and laboratory capabilities
• Cost-effectiveness for the specific setting

Implementation Requirements

• Tests must be performed according to FDA-approved protocols
• Laboratory must comply with Clinical Laboratory Improvement Amendment (CLIA) standards
• Blood collection must be arranged prior to specimen collection to ensure proper handling
• Both qualitative interpretation and quantitative measurements should be reported 1

IGRAs represent a significant advancement in tuberculosis diagnostics, offering improved specificity over TST while maintaining good sensitivity for detecting M. tuberculosis infection, particularly in BCG-vaccinated individuals and certain high-risk populations.