Mycobacterium Tuberculosis Antigen-Specific Interferon-Gamma Release Assay
Aka: Mycobacterium Tuberculosis Antigen-Specific Interferon-Gamma Release Assay, Tuberculosis Antigen-Specific Interferon-Gamma Release Assay, IGRA, IFN-Gamma Release Assay, Quantiferon-TB, QFIT-GIT, T-SPOT
II. Indications
- Mycobacterium tuberculosis testing
- Low risk patients
- Routine screening not recommended
- Screen only if symptoms suggest possible Tuberculosis
- High risk patients
- Low risk patients
- Cases in which IGRA is preferred over TST
- Unreliable follow-up for TST testing (homeless patients, Illicit Drug use)
- Patients with prior BCG vaccine
- Other indications
- May be indicated in health care settings, homeless shelters and prisons for suspected contacts
- Consider as pre-screening before starting immune suppressants or immune modulators (e.g. TNF agents)
III. Contraindications
- Children under age 5 years
IV. Mechanism
- Lab assay specific for prior Mycobacterium tuberculosis exposure
- Patient’s White Blood Cells are mixed with Mycobacterium tuberculosis antigens
- Prior exposure is associated with interferon-gamma release
- Detects interferon-gamma release
- Originates from memory T-cells
- Released by cells previously sensitized to Mycobacterium tuberculosis-specific proteins
V. Types: Interferon-gamma release assays (IGRA)
- Quantiferon-TB Gold-In-Tube Test
- Detects antigens ESAT-6, CFP-10, TB7.7
- Measures Interferon-gamma level via EIA whole blood in 16 hours
- Test Sensitivity: 70-91%
- Test Specificity: 95-99%
- T-SPOT TB Test
- Detects antigens ESAT-6, CFP-10
- Measures Interferon-gamma-producing cell count via EIA
- Analyzes peripheral blood mononuclear cells in 8-30 hours
- Test Sensitivity: 84-91%
- Test Specificity: 95-97%
VI. Efficacy
- False Negative tests (lower Test Sensitivity than with TST)
- Immunocompromised patients (anergy)
- Advanced disease, malnourishment or low CD4 Count
- Delayed lab testing >12 hours from time of blood draw
- Inadequate Temperature or other mishandling of lab specimen
- Lab testing too soon after exposure
- Immunocompromised patients (anergy)
- False Positive tests (higher Test Specificity than TST)
- Booster effect from EST-6 and CFP-10 antigens following PPD
- No false positives with prior BCG Vaccination
- No false positives with non-tuberculosis Mycobacterium strains
VII. Disadvantages
- Does not distinguish latent from Active Tuberculosis (same as with TST)
- Sample must be tested within 12 hours of being obtained
- Old test was more labor intensive and expensive
- Newer tests (QFT-GIT, T-SPOT) are more easily run now
- QFT-GIT is affected by immune status
- T-SPOT is not limited by immune status