IGRA

Interferon-Gamma Release Assays (IGRAs) – Blood Tests for TB Infection

Interferon-Gamma Release Assays (IGRAs) are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. They do not help differentiate latent tuberculosis infection (LTBI) from tuberculosis disease. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S:

  • QuantiFERON®-TB Gold In-Tube test (QFT-GIT)
  • T-SPOT®.TB test (T-Spot)

QuantiFERON-TB Gold Plus

The QFT-Plus test uses a peptide cocktail simulating M. tuberculosis proteins to stimulate cells in heparinized whole blood. Detection of interferon-γ (IFN-γ) by enzyme-linked immunosorbent assay (ELISA) is used to identify in vitro responses to these peptide antigens that are associated with Mycobacterium tuberculosis infection.

QuantiFERON-TB Gold Plus (QFT-Plus) is the next generation of the industry-leading IGRA for TB detection, QuantiFERON-TB Gold (QFT). QFT-Plus uses the same principle, test procedures, and reliable technology that you trust. QFT-Plus is now optimized with innovative tuberculosis-specific antigens that elicit both CD8 and CD4 T cell responses – enabling a more comprehensive assessment of cell-mediated immune response to TB infection.

QuantiFERON-TB Gold Plus provides:
  • Single visit testing
  • Highly accurate and reproducible
  • >97% specificity and >94% sensitivity
  • Convenient and objective lab-based testing
  • Innovative CD8 T cell technology, providing a more comprehensive view of the immune response to TB infection.
QFT-Plus advantages compared to the tuberculin skin test:

References

  1. Houben, R.M. and Dodd, P.J. (2016) The global burden of latent tuberculosis infection: a re-estimation using mathematical modelling. PLoS Med. 13, e1002152.
  2. Lewinsohn, D.M. et al. (2017) Official American Thoracic Society/Infectious Diseases Society of America/Centers for Disease Control and Prevention Clinical Practice Guidelines: Diagnosis of Tuberculosis in Adults and Children. Clin. Infect. Dis. 64, 111-115.
  3. QuantiFERON-TB Gold Plus (QFT-Plus) ELISA Package Insert. 1095849 Rev. 01 June 2017.

T-SPOT.TB 

The T-SPOT.TB test is a unique, single-visit blood test for tuberculosis (TB) screening, also known as an interferon gamma release assay (IGRA). The T-SPOT.TB test has demonstrated in a pivotal clinical study both sensitivity and specificity exceeding 95% and reliability in all at-risk groups.¹ The T-SPOT.TB blood test does not cross react with the BCG vaccine and there is no association between T-SPOT.TB blood test results and immunocompromised status.¹

According to the Centers for Disease Control and Prevention (CDC) guidelines, IGRAs (e.g. the T-SPOT.TB test) may be used in place of a TST in most situations and are preferred for BCG vaccinated individuals and for those persons who are unlikely to return for the reading of the test results.²

How the T-SPOT.TB test works:

The T-SPOT.TB  test enumerates the response of effector T cells that have been sensitized to Mycobacterium tuberculosis.

The T-SPOT.TB  test:

  • Removes background interferon gamma to maximize sensitivity
  • Utilizes a standard number of PBMCs to correct for a patient’s immune status
  • Uses a standard green top collection tube
  • Does not require special phlebotomy
The Science Behind T-SPOT Technology

Benefits of T-SPOT.TB testing:

The T-SPOT.®TB  test for tuberculosis (TB) detection is an accurate, reliable and simple method of tuberculosis screening that requires only one visit. Learn about the benefits of the T-SPOT.TB  test below:

  • ACCURATE: The T-SPOT.TB test has a sensitivity and specificity exceeding 95% in pivotal clinical trials1
  • RELIABLE: Even in challenging populations, including foreign-born and immunosuppressed¹
  • SIMPLE: One visit, one tube
  • SAVES MONEY: Hundreds of institutions have already seen how
  • COVERED BY MOST INSURANCE: CPT® Code 86481
Interpreting Tuberculosis Test Results with the T-SPOT.TB test:
  • Interferon-gamma is captured and presented as spots from T cells sensitized to TB infection
  • Results are interpreted by subtracting the spot count in the negative (NIL) control from the spot count in Panels A and B
    • Positive > 8 spots
    • Negative < 4 spots
    • Borderline 5, 6, or 7 spots
    • Invalid

How it Differs

T-SPOT.TB  test vs. 100-year-old Tuberculin Skin Test (TST)
T-SPOT.TB  Test
Tuberculin Skin Test
A single visit is required Yes No; requires at least two visits
No return visit for results Yes No; requires a return visit for reading in
48-72 hours
TB test with high sensitivity1 Yes No; limited sensitivity, especially in the immunosuppressed2
TB test with high specificity1 Yes No; limited specificity²
Does not cross react with most non-tuberculosis mycobacteria1 Yes No; cross reacts with several non-tuberculosis mycobacteria²
Objective test results Yes No; subjectivity with interpretation of results
Comparison of IGRAs
T-SPOT.TB  Test
In-Tube
Standard blood collection tubes are used Yes No; requires three specialized tubes drawn in specific order.
Blood collection tube is filled using standard phlebotomy practices Yes No; specialized tubes must be filled between 0.8mL and 1.2mL or within the black mark on the side of the tube label.³  Over  or under-filling of the tubes outside the range may lead to erroneous results.4
Phlebotomist gently inverts blood tube after drawing specimen, consistent with standard phlebotomy practices Yes No; once filled, each tube must be mixed by shaking 10 times.³  Over-energetic shaking should be avoided to minimize erroneous results due to gel dislodgement.³
Butterfly needles may be used without the need for a “purge” tube Yes No; when a butterfly needle is used, a purge tube should be used to fill the tubing with blood prior to filling the Nil tube.³
A borderline zone is used, consistent with the recommendations of the 2010 CDC Guidelines Yes No; “Although not included in FDA-approved interpretation criteria for
QFT-GIT…an appropriate borderline category for QFT-GIT might increase its accuracy…”5
Specimens can be maintained at room temperature for up to 32 hours Yes No; tubes must be transferred to an incubator as soon as possible but within 16 hours.³

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¹Oxford Immunotec. T-SPOT.TB Package Insert PI-TB-US-V6. Abingdon, UK. May 2017.
2 Huebner R et al., The tuberculin skin test. Clin Infect Dis  1993; 17: 968-975.
3 Cellestis Technical Note, L05995036B
4 QuantiFERON®-TB Gold Package Insert, page 9; Doc. No. US05990301J
5 MMWR 2010;59(RR-5):1-25.
T-SPOT is a registered trademark of Oxford Immunotec Ltd.
QFT is a registered trademark of The Qiagen Group.