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Microbiology · Immunology: interferon-gamma release assay interpretation
Sample itemA 35-year-old man with advanced HIV (CD4 count 40 cells/mm3) is screened for latent tuberculosis. The interferon-gamma release assay reports an indeterminate result because the positive mitogen control produced little interferon-gamma. How should this be interpreted?
Original practice item, not a recalled exam question. Nothing here is recorded.
The answer and the reasoning
A. Uninterpretable, because failure of the mitogen control reflects poor T-cell response and does not exclude infection
The assay measures interferon-gamma released by sensitised T cells after stimulation with ESAT-6 and CFP-10, with a mitogen as positive control. A low mitogen response, common in severe lymphopenia, shows the T cells cannot respond, so a negative antigen response cannot be trusted. Such results are reported as indeterminate and should be repeated or supplemented by clinical assessment.
Option by option
A. Uninterpretable, because failure of the mitogen control reflects poor T-cell response and does not exclude infection (correct)
A failed positive control makes the test invalid, so latent infection is neither confirmed nor excluded.
B. Negative, because the tuberculosis antigens produced no response and infection is excluded
A negative result requires an adequate mitogen response, which is absent here.
C. Positive for non-tuberculous mycobacterial infection
These antigens are present in Mycobacterium tuberculosis and a few species such as M. kansasii and M. marinum, and this indeterminate result does not identify any species.
D. Positive, because background interferon-gamma is raised from BCG vaccination
ESAT-6 and CFP-10 are absent from BCG, so BCG does not produce a positive result.
Source note: Original NextPrep sample item — pending expert review. This item is original practice material awaiting independent expert review, so confirm important facts in a standard textbook.
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