What does an “indeterminate” result in QuantiFERON Gold in-Tube test for latent tuberculosis really mean?

Anindeterminate” QuantiFeron Gold in-Tube (QFT-IT) simply means the result can’t be interpreted. It does NOT mean “intermediate” or “borderline positive”!

Although there are several reasons for an indeterminate QFT-IT, a common explanation is an immunocompromised state involving inadequate T-cell response (eg, corticosteroids, HIV, cancer). Improper storage of tubes and specimen handling, baseline elevated interferon (IFN)-ɣ due to heterophile antibodies, recovery phase of an infection or vaccination may also be associated with indeterminate QFT-IT results. 1,2 For these reasons, the test should be repeated for confirmation.

It all makes more sense if we understand the basis for the test. QFT-IT involves blood obtained in 3 separate test tubes:

  • Tube 1: Contains only the patient’s blood with nothing added (NIL) (“Negative control”)
  • Tube 2: Contains non-specific mitogens that stimulate patient’s T-cells (“Positive control”)
  • Tube 3: Contains specific TB antigens

Since QFT-IT is an IFN- ɣ release assay, IFN- ɣ is measured in each tube after 16-24 h incubation. A negative QFT-IT is when there is not much difference between IFN- ɣ levels in negative control and TB tubes (“TB-[minus]NIL”) AND the positive control works (“MITOGEN-[minus]NIL” is elevated).

You can now see why a negative result in the TB tube doesn’t mean much (ie, the result is “indeterminate”) when the T-cells don’t respond to non-specific antigens.  This situation is analogous to calling a PPD “negative” when a patient is anergic!

References

  1. Herrera V, Yeh E, Murphy K, et al. Immediate incubation reduces indeterminate results for QuantiFERON-TB Gold in-Tube assay. J Clin Microbiol 2010;48:2672-2676. http://jcm.asm.org/content/48/8/2672.full
  2. Bui DHP, Cruz AT, Graviss EA. Indeterminate QuantiFERON-TB Gold in-Tube assay results in children. Ped Infect Dis J 2014; 33: 220-22. https://www.ncbi.nlm.nih.gov/pubmed/24413410
What does an “indeterminate” result in QuantiFERON Gold in-Tube test for latent tuberculosis really mean?

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