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

Purpose of Interferon-Gamma Release Assays (IGRAs)

Interferon-Gamma Release Assays (IGRAs) are blood tests designed to detect Mycobacterium tuberculosis infection by measuring interferon-gamma release in response to M. tuberculosis-specific antigens, serving as aids in diagnosing both latent tuberculosis infection (LTBI) and active tuberculosis disease. 1, 2

Primary Functions of IGRAs

• IGRAs detect sensitization to M. tuberculosis by measuring interferon-gamma (IFN-γ) release in response to antigens representing M. tuberculosis, providing an alternative to the tuberculin skin test (TST) 1
• IGRAs may be used in all situations where the tuberculin skin test is recommended, including contact investigations and evaluation of recent immigrants 2
• IGRAs serve as aids in diagnosing M. tuberculosis infection, both latent infection and infection manifesting as active tuberculosis 1
• IGRAs are valuable for surveillance purposes and to identify persons likely to benefit from treatment for latent tuberculosis infection 1, 2

Advantages of IGRAs Over TST

• IGRAs use M. tuberculosis-specific antigens (ESAT-6, CFP-10, and TB7.7) that are absent from BCG vaccine strains and most nontuberculous mycobacteria, providing improved specificity compared to TST 1, 2
• IGRAs are not affected by prior BCG vaccination, which reduces false-positive results commonly seen with TST in vaccinated populations 2, 3
• IGRAs require only one patient visit for blood collection, eliminating the need for return visits for test reading as required by TST 2, 3
• IGRAs include internal positive controls (mitogen) to assess immune function, which helps identify potentially false-negative results due to immunosuppression 1, 3

Types of FDA-Approved IGRAs

• Two commercial IGRAs are currently FDA-approved in the United States: 1
  • QuantiFERON-TB Gold In-Tube test (QFT-GIT) - uses an ELISA method to measure IFN-γ concentration in response to M. tuberculosis antigens 1, 3
  • T-SPOT.TB test (T-Spot) - uses an ELISpot method to enumerate IFN-γ-secreting T cells 1, 3

Limitations of IGRAs

• Like the TST, IGRAs cannot distinguish between active TB disease and latent TB infection 2, 4
• Neither IGRAs nor TST can discriminate between current or past M. tuberculosis infection 4, 5
• Sensitivity and specificity of IGRAs vary across different clinical contexts and populations 2, 5
• IGRAs may be affected by certain immunosuppressive conditions or medications, though generally less than TST 2, 5

Recommended Approaches to IGRA Implementation

• Several approaches for IGRA use are recommended in guidelines: 1, 2
  • Two-step approach: TST first, followed by IGRA either when TST is negative (to increase sensitivity, especially in immunocompromised individuals) or when TST is positive (to increase specificity, especially in BCG-vaccinated individuals) 1, 2
  • Either TST or IGRA alone, but not both 1
  • IGRA and TST together to increase sensitivity 1, 2
  • IGRA only, replacing the TST 1

Clinical Applications

• IGRAs are particularly useful in BCG-vaccinated individuals to avoid false-positive results that commonly occur with TST 2, 3
• In high TB incidence settings, IGRAs are most valuable for screening high-risk groups 2
• In low TB incidence countries, detection and management of LTBI using IGRAs is a key component of TB control 1, 2
• IGRAs may be less affected by high-dose steroid therapy compared to TST, which can be suppressed by such treatment 2

Emerging Research

• Recent research is exploring the use of additional biomarkers beyond IFN-γ, such as IP-10, to potentially distinguish between active TB and LTBI 6, 7
• The ratio of TB-specific to mitogen-induced IP-10 responses has shown promise for discriminating active TB versus LTBI with high sensitivity and specificity 7