title: Discrepancy between Mycobacterium tuberculosis-specific gamma interferon release assays using short and prolonged in vitro incubation.
abstract: 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 (kappa = 0.71) and between TST and LST (kappa = 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.
authors.affiliation: Department of Infectious Diseases, C5P, Leiden University Medical Center, RC Leiden, The Netherlands.
authors.forename: Eliane M S
authors.initials: EM
authors.lastname: Leyten
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Arend
authors.forename: Corine
authors.initials: C
authors.lastname: Prins
authors.forename: Frank G J
authors.initials: FG
authors.lastname: Cobelens
authors.forename: Tom H M
authors.initials: TH
authors.lastname: Ottenhoff
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D000328:Adult; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods* / Q000592:standards; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000378:metabolism*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008828:Microbiological Techniques / Q000592:standards; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology* / Q000302:isolation & purification*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D014374:Tuberculin Test / Q000592:standards; D014397:Tuberculosis, Pulmonary / Q000175:diagnosis* / Q000276:immunology
chemical_list: D007371:Interferon-gamma