IGRA

Understanding the Results of the IGRA QFT-Gold Plus Test

09 June 2023

We appreciate your confidence in selecting Prodia for the Interferon-Gamma Release Assay (IGRA) test. This page aims to comprehensively explain the IGRA test results at Prodia. At Prodia, IGRA is one of the available tuberculosis (TB) diagnostic tests. Within the IGRA test results, doctors can observe five outcomes: IGRA qualitative results, TB1 Ag minus Nil, TB2 Ag minus Nil, mitogen minus Nil, and NIL value.

The IGRA tests can detect both active TB and Latent Tuberculosis Infection (LTBI). The QuantiFERON-TB Gold Plus analyzes the interferon-gamma (IFN-γ) released by CD4+ lymphocytes after in vitro stimulation with TB-specific antigens (ESAT-6 and CFP-10). Currently, Prodia employs a new formulation of ESAT-6/CFP-10 peptides in two tubes for the IGRA QuantiFERON-TB Gold Plus (QFTPlus), namely tube 1 (TB1) and tube 2 (TB2). Both tubes contain peptide antigens from the MTB-complex-associated antigens, ESAT-6 and CFP-10. The TB1 tube contains peptides from ESAT-6 and CFP-10 that are designed to elicit CMI responses from CD4+ T-helper lymphocytes, while the TB2 tube includes an additional set of peptides to induce the Cell-Mediated Immune (CMI) responses from CD8+ cytotoxic T lymphocytes. On the QFT-Plus tests, whole blood is collected into each of the QFT-Plus tubes, which include a Nil tube, TB1 tube, TB2 tube, and Mitogen tube (1, 2, 3). Using four tubes––Nil, mitogen-nil, TB1-NIL, and TB2-NIL––provides four different results on the tools, each explained below:

1. The Nil assesses whether a patient possesses pre-existing immune responses that could potentially lead to a false-positive result. The NIL value in the result indicates nonspecific reactivity in the patient’s specimens.

2. Mitogen ensures the adequate immune status and activity of patient lymphocytes, while also overseeing compliance throughout the process of sampling and sample incubation. The results are instrumental in detecting false-negative readings. The mitogen minus Nil value serves as a positive control to assess lymphocyte activity in patient specimens.

3. The TB antigen tubes are coated with Mycobacterium tuberculosis.  The TB1-NIL value in the results particularly detects the reactivity of CD4+ lymphocytes, specifically stimulated by the TB1 antigen. The TB2-NIL value in the results identifies the reactivity of both CD4+ and CD8+ lymphocytes stimulated by the TB2 antigen.
 

The QFT-Plus results are interpreted based on the following criteria:

The measured level of IFN-γ does not correlate with the stage or severity of infection, the level of immune responsiveness, or the likelihood of progressing to active disease. It is uncommon to observe a positive TB response in individuals who test negative for Mitogen, but such instances have been noted in patients diagnosed with TB disease. This suggests that the IFN-γ response to TB Antigen surpasses that to Mitogen, which is plausible given that the level of Mitogen does not maximally stimulate IFN-γ production by lymphocytes (4).

Sumber
  1. Hoffmann H. Hoffmann, Avsar K, Gores R, Mavi SC,  Hofmann-Thiel S. Equal sensitivity of the new generation QuantiFERON-TB Gold plus in direct comparison with the previous test version QuantiFERON-TB Gold IT. Clin. Microbiol. Infect. 2016; 22: 701. 
  2. Yi L, Sasaki Y, Nagai H, Ishikawa S, Takamori M, Sakashita K, et al. Evaluation of QuantiFERON-TB Gold Plus for detection of Mycobacterium tuberculosis infection in Japan. Sci. Rep. 2016; 6: 30617.
  3. Barcellini L, Borroni E, Brown J, Brunetti E, Campisi D, Castellotti PF, et al. First evaluation of QuantiFERON-TB Gold Plus performance in contact screening. Eur. Respir. J. 2016; 48: 1411. 
  4. QuantiFERON®-TB Gold Plus (QFT -Plus) ELISA Package rfInsert. 1095849 Rev. 01 June 2017.