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Clinical and Vaccine Immunology, July 2007, p. 880-885, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00132-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Discrepancy between Mycobacterium tuberculosis-Specific Gamma Interferon Release Assays Using Short and Prolonged In Vitro Incubation

Eliane M. S. Leyten,^1, Sandra M. Arend,^1* Corine Prins,¹ Frank G. J. Cobelens,³ Tom H. M. Ottenhoff,^1,2 and Jaap T. van Dissel¹

Department of Infectious Diseases,¹ Department of Immunohematology and Blood Transfusion, Leiden University Medical Center, Leiden, The Netherlands,² KNCV Tuberculosis Foundation, The Hague, The Netherlands³

Received 23 March 2007/ Returned for modification 12 April 2007/ Accepted 7 May 2007

The sensitivities of various gamma interferon release assays (IGRAs) for the detection of past latent Mycobacterium tuberculosis infection are not known. In this study, we aimed to assess the effects of various IGRA formats and in vitro incubation periods on test outcome. The results of the tuberculin skin test (TST) were compared with those of the QuantiFERON-TB Gold in-tube (QFT-GIT) test, an overnight enzyme-linked immunospot assay (ELISPOT), and a 6-day lymphocyte stimulation test (LST) by using the same M. tuberculosis-specific peptides and samples from 27 TST-positive persons with a history of exposure to M. tuberculosis, 4 patients cured of tuberculosis (TB), and 9 TST-negative controls. Among the TST-positive persons, the LST was more frequently positive (92%; P < 0.01) than either the QFT-GIT test (33%) or ELISPOT (46%). While good agreement was observed between the QFT-GIT test and ELISPOT ( = 0.71) and between TST and LST ( = 0.78), the agreement between TST or LST, on the one hand, and the QFT-GIT test or ELISPOT, on the other, was poor. These data indicate that the QFT-GIT test and overnight ELISPOT are less sensitive for the detection of past latent TB than the 6-day LST. The observed discrepancies between these IGRAs are most likely related to differences in incubation periods. Whether TST-positive persons with positive LST results but negative QFT-GIT and ELISPOT results are at risk for the development of TB needs to be elucidated before short-incubation IGRAs can be used for the screening of individuals for latent TB before immunosuppressive treatment.

Published ahead of print on 16 May 2007.

Present address: Department of Internal Medicine, Medisch Centrum Haaglanden, Lijnbaan 32, 2512 VA, The Hague, The Netherlands.

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