Interferon Gamma Release Assay (IGRA) – Overview
The Interferon Gamma Release Assay (IGRA) is a blood test used to detect tuberculosis infection by measuring the immune response to specific TB antigens.
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The Interferon Gamma Release Assay (IGRA) is a blood test used to detect tuberculosis infection by measuring the immune response to specific TB antigens.
What Is the Interferon Gamma Release Assay?
The Interferon Gamma Release Assay (IGRA) is a modern blood-based diagnostic test used to detect infection with Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Unlike the traditional tuberculin skin test (TST), the IGRA is performed entirely in a laboratory using a blood sample, which makes it more precise and less susceptible to interpretation errors.
The test is particularly valuable for diagnosing latent tuberculosis infection (LTBI), a condition in which the TB bacterium is present in the body but causes no active symptoms. Well-known commercially available IGRA tests include QuantiFERON-TB Gold and T-SPOT.TB.
Mechanism of Action
In the IGRA, a blood sample is drawn from the patient and incubated in the laboratory with specific antigens derived from Mycobacterium tuberculosis – most notably ESAT-6 and CFP-10. If the patient has previously been exposed to the TB bacterium, their T-lymphocytes (white blood cells) will recognize these antigens and release interferon-gamma (IFN-γ), an important signaling molecule of the immune system.
The quantity of IFN-γ released is then measured. An elevated level is considered indicative of prior infection with M. tuberculosis. Because the antigens used (ESAT-6, CFP-10) are not present in the BCG vaccine strain (Bacillus Calmette-Guérin), the IGRA produces reliable results even in individuals who have been vaccinated with BCG.
Clinical Applications
- Diagnosis of latent tuberculosis infection (LTBI)
- Screening of high-risk groups (e.g., close contacts of TB patients, immunocompromised individuals, healthcare workers)
- Pre-screening before starting immunosuppressive therapy (e.g., TNF-alpha inhibitors or biologics)
- Immigrant screening in low-TB-prevalence countries
- Supplementary diagnostic tool in cases of suspected active tuberculosis
How the Test Is Performed
The IGRA is straightforward to perform. A venous blood sample is drawn from the patient and transferred into specially prepared tubes containing TB-specific antigens. After an incubation period of typically 16 to 24 hours, the concentration of interferon-gamma in the blood is measured using an ELISA (Enzyme-Linked Immunosorbent Assay) or a comparable method.
In the T-SPOT.TB test, an alternative approach is used: the number of IFN-γ-secreting T-cells is counted using an ELISPOT method. Results are generally available within 24 to 48 hours.
Interpretation of Results
- Positive result: Suggests prior infection with M. tuberculosis. This may indicate latent infection or, in combination with other clinical findings, active tuberculosis.
- Negative result: Argues against infection, but does not entirely exclude it (e.g., in very recent infection or severe immunosuppression).
- Indeterminate result: May occur due to a very weak immune response or technical issues; in such cases, repeating the test is recommended.
Advantages Over the Tuberculin Skin Test
- Not influenced by prior BCG vaccination
- Only a single patient visit is required (no need for a follow-up reading appointment)
- Higher specificity in BCG-vaccinated individuals
- Less susceptible to subjective interpretation
Limitations
The IGRA cannot reliably distinguish between latent and active tuberculosis on its own. In severely immunocompromised patients (e.g., individuals with HIV and very low CD4 cell counts), the sensitivity of the test may be reduced. Additionally, the test requires proper laboratory infrastructure and is more costly compared to the tuberculin skin test.
References
- World Health Organization (WHO): Latent tuberculosis infection: updated and consolidated guidelines for programmatic management. Geneva: WHO, 2018. Available at: https://www.who.int
- Centers for Disease Control and Prevention (CDC): Tuberculosis (TB) – Interferon-Gamma Release Assays (IGRAs) – Blood Tests for TB Infection. Atlanta: CDC, 2023. Available at: https://www.cdc.gov
- Pai M, Denkinger CM, Kik SV et al.: Gamma Interferon Release Assays for Detection of Mycobacterium tuberculosis Infection. Clinical Microbiology Reviews, 2014; 27(1): 3–20.
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