What is the interpretation of two IGRAs with negative mitogen wells, in the absence of immunosuppression?

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 means that: The lab mishandled her PBMC twice. Something is wrong with her cellular immune system. Other. 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. TB therapy should be started empirically. This result is not evidence of prior TB infection. Despite recent chemo, the IGRA should be repeated. Need more information. Other.

3 Answers

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Infectious Disease · Cooperman Barnabas Medical Center

Answered on

If I understand this case correctly, the patient is actively ill and the patient's doctors are considering tuberculosis as a possible etiology of the patient's illness. In that scenario, IGRAs and PPDs have a limited to no role. Epidemiology, family history, and other possible exposures do. In your case, the negative mitogen wells are probably the result of the patient's acute illness, whatever the cause.

Selective anergy was a term used to describe a negative PPD in a patient with active TB an...

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Infectious Disease · University of Rochester School of Medicine and Dentistry

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In both scenarios, you have an indeterminate test result. Even without immunosuppression a small fraction of people have indeterminate results, and in active TB that percentage is larger.

In scenario 1, if you are concerned about active TB based on exposure or epidemiology, you should pursue testing with CXR, CT chest, sputum, blood AFB isolator tube, etc. depending on the site of infection. If no risk factors for TB, would pursue other infectious and non-infectious sources.

In scenario 2, a pos...

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Infectious Disease · University of Louisville Health Sciences Center

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An IGRA mitogen well serves as a positive control. The nil well detects what I call interfering immunologic activity. It is supposed to be greater than or equal to 8.0 IU/mL to be considered valid. The value (assuming it is less than or equal to 8) is subtracted from the TB well before the TB value is reported.

The fact that the mitogen well in both of these scenarios is negative is suspect in both cases. In the first case, it would be rare that a lab would make this error twice, but if it did h...

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