Quantitative T-cell interferon-gamma responses to Mycobacterium tuberculosis-specific antigens in active and latent tuberculosis

Abstract

The objective was to compare the quantitative T-cell responses measured by the commercial interferon-gamma (IFNgamma) release assays (IGRAs) in active and latent tuberculosis (TB) states. T-cell responses of culture-proven TB cases were compared with those of contacts with positive IGRA results and tuberculin skin tests >or= 15 mm. T-SPOT.TB results in 270 active TB cases and 183 community contacts showed the median spot-forming cells (SFCs) above negative control/2.5 x 10(5) peripheral blood mononuclear cells to be 27 (-1 to 203) vs 10 (-2 to 174) in response to ESAT-6 (p < 0.001); and 37 (0 to 293) vs 13 (0 to 225) to CFP-10 (p < 0.001). The median IFNgamma levels (antigen minus nil control) as measured by QuantiFERON-TB Gold In-tube in 270 cases and 142 contacts in congregate settings was 2.3 IU/ml (-0.58 to 31.44) vs 1.7 IU/ml (0.35 to 26.51, p = 0.98). Quantitative T-cell responses as measured by the T-SPOT.TB may indicate mycobacterial burden and disease activity, but cannot be used to discriminate active from latent TB.

Quantitative Comparison of Active and Latent Tuberculosis in the Cynomolgus Macaque Model

“…The increased production of mycobacterium-specific IFN-␥ found in BAL, lymph node, and PBMC among activedisease monkeys likely reflects the increased bacterial burden among this group. Similarly, the greater production of IFN-␥ from PBMCs in humans with active disease compared to that of latently infected individuals has been documented (4,10,11,13,14,19,26). In each of the studies, a wide range of results is demonstrated within each clinical group (active versus latent), reflecting a wide spectrum of disease associated with each clinical classification that also is seen in our model.…”

Increased risk of tuberculosis after gastrectomy and chemotherapy in gastric cancer: a 7-year cohort study

“…However, a lack of evidence for latent status is a limitation of the present study. Further immunological tests, including interferon gamma release assay (IGRA) tests [23][24][25][26][27] and follow-up should be conducted, although the role of interferon-gamma in high-burden areas remains controversial [28]. In the present survey, 14.5% of the patients did not have available chest film images, and 8 of them had TB after gastric cancer treatment.…”

Immunodiagnosis of Tuberculosis: a Dynamic View of Biomarker Discovery

“…Studies with experimentally infected animals support this possibility (5). Indeed, many studies conducted with IGRAs have shown higher IFN-␥ responses in active TB patients than in LTBI cases (17,73,74,164). Discordant results, however, have also been obtained (113).…”

“…Discordant results, however, have also been obtained (113). The disease-associated increase seems to be more evident with the enzyme-linked immunospot (ELISPOT) assay, an assay enumerating IFN-␥-producing cells, than with enzyme-linked immunosorbent assay (ELISA), which measures the levels of IFN-␥ secreted by the cultured cells (17,18,39,40,79,80,118). Thus, the two assays may have different sensitivities.…”