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Clinical Trial
. 2009 Feb 28:9:23.
doi: 10.1186/1471-2334-9-23.

T-SPOT.TB responses during treatment of pulmonary tuberculosis

Samantha Ribeiro  1 , Kelly Dooley, Judith Hackman, Carla Loredo, Anne Efron, Richard E Chaisson, Marcus B Conde, Neio Boechat, Susan E Dorman
Affiliations
Clinical Trial

T-SPOT.TB responses during treatment of pulmonary tuberculosis

Samantha Ribeiro et al. BMC Infect Dis. .

Abstract

Background: Immune responses to Mycobacterium tuberculosis antigens could serve as surrogate markers of treatment response.

Methods: Using the T-SPOT.TB assay and frozen peripheral blood mononuclear cells, we enumerated ESAT-6- and CFP-10-specific IFN-gamma-producing T cells over time in pulmonary TB patients receiving directly observed treatment. T cell responses (measured as "spot forming cells" or "SFCs") were assessed prior to treatment and at 16 and 24 weeks of treatment.

Results: 58 patients were evaluated, of whom 57 were HIV seronegative. Mean (SD) ESAT-6, CFP-10, and summed RD1 specific SFCs declined from 42.7 (72.7), 41.2 (66.4), and 83.8 (105.7) at baseline to 23.3 (39.4, p = 0.01), 23.2 (29.4, p = 0.18), and 46.5 (59.5, p = 0.02) at completion of 24 weeks of treatment, respectively. Only 10% of individuals with a baseline reactive test reverted to negative at treatment week 24. For the group that was culture positive at completion of 8 weeks of treatment compared to the culture negative group, the incidence rate ratio (IRR) of ESAT-6, CFP-10, and summed RD1 specific SFC counts were, respectively, 2.23 (p = 0.048), 1.51 (p = 0.20), and 1.83 (p = 0.047). Patients with cavitary disease had mean ESAT-6 specific SFC counts that were higher than those without cavitary disease (IRR 2.08, p = 0.034).

Conclusion: IFN-gamma-producing RD1-specific T cells, as measured in the T-SPOT.TB assay, may be directly related to bacterial load in patients undergoing treatment for pulmonary TB. However, high inter-subject variability in quantitative results coupled with failure of reversion to negative of qualitative results in most subjects at treatment completion may limit the utility of this assay as a surrogate marker for treatment efficacy.

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Figures

Figure 1
Figure 1
Mean ESAT-6, CFP-10, and summed RD1 specific spot forming cells at weeks 0 (baseline), 16, and 24 for all study participants (n = 58). SFC, spot forming cells. Vertical bars represent standard deviations of the means.
Figure 2
Figure 2
Individual patient RD1 spot forming cell response profiles over 24 weeks of TB treatment for individuals having a negative sputum culture for M. tuberculosis at completion of 8 weeks of TB treatment (PANEL A, n = 48), and for individuals having a positive sputum culture at completion of 8 weeks of TB treatment (PANEL B, n = 10). SFC, spot forming cells.
Figure 3
Figure 3
Mean ESAT-6, CFP-10, and summed RD1 specific spot forming cells at weeks 0 (baseline), 16, and 24 for individuals having a positive sputum culture for M. tuberculosis at completion of 8 weeks of TB treatment (SOLID BARS, n = 10), and for individuals having a negative sputum culture at completion of 8 weeks of TB treatment (HATCHED BARS, n = 48). SFC, spot forming cells. Vertical bars represent standard deviations of the means.
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