Limits...
T-SPOT.TB responses during treatment of pulmonary tuberculosis.

Ribeiro S, Dooley K, Hackman J, Loredo C, Efron A, Chaisson RE, Conde MB, Boechat N, Dorman SE - BMC Infect. Dis. (2009)

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Doenças do Torax/Hospital Clementino Fraga Filho/Universidade Federal do Rio de Janeiro, Brazil. sbrmicroimuno@yahoo.com.br

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.

Show MeSH

Related in: MedlinePlus

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2651889&req=5

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.

Mentions: Next, we compared SFC counts between individuals who remained sputum culture positive at completion of 8 weeks of treatment and individuals who were sputum culture negative at completion of 8 weeks of treatment. Forty-eight (82.8%) of 58 individuals were culture negative at 8 weeks, and 10 (17.2%) of 58 remained culture positive. As shown in Figure 2, individual participant RD1 SFC response profiles demonstrated large intersubject and intrasubject variability. Mean SFC counts are shown in Figure 3. Compared with subjects having negative culture results, culture positive subjects had higher mean SFC counts at all time points and for both ESAT-6 and CFP-10. Mean ESAT-6 SFC count was on average 2.23 times higher for the group that was culture positive at completion of 8 weeks of treatment than for the group that was culture negative (IRR 95% CI 1.01 to 4.93, p = 0.048). The mean CFP-10 SFC count was on average 1.51 times higher for the culture positive group compared to the culture negative group, but this difference did not reach statistical significance (IRR 95% CI 0.80 to 2.85, p = 0.20). The mean RD1 SFC count was on average 1.83 times higher for the culture positive group compared to the culture negative group (IRR 95% CI 1.01 to 3.33, p = 0.047); the rate of decline did not differ between the two groups (p = 0.54). At completion of 24 weeks of therapy, the culture positive group had ESAT-6 and CFP-10 counts that were 2.27 (IRR 95% CI 0.82 to 6.31) and 2.36 (IRR 95% CI 0.92 to 6.04) times higher than the culture negative group, but neither of these differences reached statistical significance.


T-SPOT.TB responses during treatment of pulmonary tuberculosis.

Ribeiro S, Dooley K, Hackman J, Loredo C, Efron A, Chaisson RE, Conde MB, Boechat N, Dorman SE - BMC Infect. Dis. (2009)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651889&req=5

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.
Mentions: Next, we compared SFC counts between individuals who remained sputum culture positive at completion of 8 weeks of treatment and individuals who were sputum culture negative at completion of 8 weeks of treatment. Forty-eight (82.8%) of 58 individuals were culture negative at 8 weeks, and 10 (17.2%) of 58 remained culture positive. As shown in Figure 2, individual participant RD1 SFC response profiles demonstrated large intersubject and intrasubject variability. Mean SFC counts are shown in Figure 3. Compared with subjects having negative culture results, culture positive subjects had higher mean SFC counts at all time points and for both ESAT-6 and CFP-10. Mean ESAT-6 SFC count was on average 2.23 times higher for the group that was culture positive at completion of 8 weeks of treatment than for the group that was culture negative (IRR 95% CI 1.01 to 4.93, p = 0.048). The mean CFP-10 SFC count was on average 1.51 times higher for the culture positive group compared to the culture negative group, but this difference did not reach statistical significance (IRR 95% CI 0.80 to 2.85, p = 0.20). The mean RD1 SFC count was on average 1.83 times higher for the culture positive group compared to the culture negative group (IRR 95% CI 1.01 to 3.33, p = 0.047); the rate of decline did not differ between the two groups (p = 0.54). At completion of 24 weeks of therapy, the culture positive group had ESAT-6 and CFP-10 counts that were 2.27 (IRR 95% CI 0.82 to 6.31) and 2.36 (IRR 95% CI 0.92 to 6.04) times higher than the culture negative group, but neither of these differences reached statistical significance.

Bottom Line: 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).

View Article: PubMed Central - HTML - PubMed

Affiliation: Instituto de Doenças do Torax/Hospital Clementino Fraga Filho/Universidade Federal do Rio de Janeiro, Brazil. sbrmicroimuno@yahoo.com.br

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.

Show MeSH
Related in: MedlinePlus