What is the interpretation of an IGRA with positive TB wells and negative nil and negative mitogen wells?

A patient on meloxicam for LBP developed high, persistent fevers and no other symptoms. An IGRA, among many tests, was sent. The IGRA’s mitogen well was negative (the TB and nil wells were negative as well). 8 days later, the IGRA was repeated and again, all wells, including the mitogen well, were negative. Does the fact that her PBMC, when exposed to a mitogen, on two separate tests done 8 days apart by a large, commercial lab mean that the lab mishandled her PBMC twice or something is wrong with her cellular immune system? A patient, who was epidemiologically at risk for prior TB infection, had an IGRA prior to receiving immunosuppressive chemotherapy. The nil and mitogen wells did not produce significant amounts of IFN-γ, but her TB wells did. The lab interpreted this test as indeterminate. A follow-up test was not sent. How should this result be interpreted? Of relevance, at this time, the patient was receiving chemo, had markedly elevated WBC and fever of unknown origin.

2 Answers

Mednet Member

Infectious Disease · Cooperman Barnabas Medical Center

Answered on

We don't see positive controls in most clinical assays. They are run, of course, but hidden from view. The mitogen well is the positive control in the IGRAs. The mitogen used QuantiFERON-TB Gold is, I believe, PHA or phytohemagglutinin. PHA turns on T-cells to indiscriminately. If I remember my mitogen MOAs, PHA binds to the T-cell receptor outside of the binding site and turns on 30% or more of human T-cells.

I have seen many misinterpretations of IGRAs by doctors, including some ID doctors. The most common mistake is thinking "indeterminate" = "intermediate". Indeterminate means that the mitogen well didn't produce enough gIFN. Said another way, Indeterminate means that the positive control wasn't positive. The mitogen well, as Dr. @Dr. F...

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Mednet MemberInvited Expert

Infectious Disease · Harbor-UCLA Medical Center

Answered on

In the setting of acute inflammatory illness, I would interpret the tests results as indeterminate, regardless of the amounts of interferon produced. In an acutely ill immunocompromised patient, the IGRA is often indeterminate, as they have inadequate immune responses. Similarly, a negative TST placed in this situation does not rule out past (or current) TB infection.

IGRAs do not diagnose TB; clinicians diagnose TB. If your clinical suspicion is high enough based on clinical syndrome, radiology, and microbiology, you should treat.

To help risk stratify, I find tstin3d.com useful for evaluating pre-test probability of TB. Of course, that's just one piece of information.

Which type of IGRA was used in this case? I would consider sending to a...

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