Unusual Interferon Gamma Measurements with QuantiFERON-TB Gold and QuantiFERON-TB Gold In-Tube Tests

Introduction: Interferon gamma (IFN-gamma) release assays, such as QuantiFERON (R)-TB Gold test (QFT-G) and QuantiFERON (R)-TB Gold In-Tube test (QFT-GIT) are designed to detect M. tuberculosis (Mtb) infection. Recognition of unusual IFN-gamma measurements may help indicate inaccurate results. Methods: We examined QFT-G and QFT-GIT results from subjects who had two or more tests completed. We classified unusual IFN-gamma measurements as: 1) High Nil Concentration (HNC) when IFN-gamma concentration in plasma from unstimulated blood exceeded 0.7 IU/mL; 2) Low Mitogen Response (LMR) when Mitogen Response was <0.5 IU/mL; 3) Very Low Mitogen Response (VLMR) when Mitogen Response was <=-0.5 IU/mL; and 4) Very Low Antigen Response (VLAR) when the response to a Mtb antigen was <=-0.35 IU/mL and <=-0.5 times the IFN-gamma concentration in plasma from unstimulated blood. Results: Among 5,309 results from 1,728 subjects, HNC occurred in 234 (4.4%) tests for 162 subjects, LMR in 108 (2.0%) tests for 85 subjects, VLMR in 22 (0.4%) tests for 21 subjects, and VLAR in 41 (0.8%) tests for 39 subjects. QFT-GIT had fewer HNC, VLMR, and VLAR (p = 0.042, 0.004, and 0.067 respectively); QFT-G had fewer LMR (p = 0.005). Twenty-four (51.6%) of 47 subjects with positive results and HNC were negative or indeterminate by all other tests. Thirteen (61.9%) of 21 subjects with positive results and LMR were negative or indeterminate by all other tests. Conclusion: Unusual IFN-gamma measurements including HNC, LMR, VLMR, and VLAR were encountered in small numbers, and in most instances were not seen on simultaneously or subsequently performed tests. To avoid erroneous diagnosis of Mtb infection, IGRAs with unusual IFN-gamma measurements should be repeated with another blood sample and interpreted with caution if they recur.