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Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.

Mitchell JE, Chetty S, Govender P, Pillay M, Jaggernath M, Kasmar A, Ndung'u T, Klenerman P, Walker BD, Kasprowicz VO - PLoS ONE (2012)

Bottom Line: During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB.Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB.The RD1-Elispot appears to have limited value in this setting.

View Article: PubMed Central - PubMed

Affiliation: Ragon Institute of MGH, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from -150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r=0.6527, p=0.0114; IP-10: r=0.6967, p=0.0056; IP-10+MIG: r=0.7055, p=0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting.

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Impact of ARVS on the RD1-specific T cell kinetic profile.Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).
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pone-0037920-g005: Impact of ARVS on the RD1-specific T cell kinetic profile.Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).

Mentions: Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).


Prospective monitoring reveals dynamic levels of T cell immunity to Mycobacterium tuberculosis in HIV infected individuals.

Mitchell JE, Chetty S, Govender P, Pillay M, Jaggernath M, Kasmar A, Ndung'u T, Klenerman P, Walker BD, Kasprowicz VO - PLoS ONE (2012)

Impact of ARVS on the RD1-specific T cell kinetic profile.Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3369919&req=5

pone-0037920-g005: Impact of ARVS on the RD1-specific T cell kinetic profile.Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).
Mentions: Figure 5 A–B: Summary of longitudinal data from 11 individuals who were placed on ARVs and had a consistent cut-off at all time-points tested. Figure 5A: Summary of ESAT-6-specific responses. Figure 5B: Summary of CFP-10-specific responses. Left-hand panel =  data from all 11 individuals. Right-hand panel =  Mean response plotted. The mean ESAT-6 spot-forming cells (SFC) at 3 months prior to ARV initiation was 7, and that for CFP-10 was 5 SFC. These responses declined to 2 SFC for ESAT-6 specific responses and 3 SFC for CFP-10 specific responses. Overall the mean response declined after the initiation of ARV therapy, however this did not reach statistical significance (ESAT-6: p = −0.1133, CFP-10: p = 0.1109 (paired t-test)).

Bottom Line: During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB.Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB.The RD1-Elispot appears to have limited value in this setting.

View Article: PubMed Central - PubMed

Affiliation: Ragon Institute of MGH, Harvard Medical School, Boston, Massachusetts, United States of America.

ABSTRACT
Monitoring of latent Mycobacterium tuberculosis infection may prevent disease. We tested an ESAT-6 and CFP-10-specific IFN-γ Elispot assay (RD1-Elispot) on 163 HIV-infected individuals living in a TB-endemic setting. An RD1-Elispot was performed every 3 months for a period of 3-21 months. 62% of RD1-Elispot negative individuals were positive by cultured Elispot. Fluctuations in T cell response were observed with rates of change ranging from -150 to +153 spot-forming cells (SFC)/200,000 PBMC in a 3-month period. To validate these responses we used an RD1-specific real time quantitative PCR assay for monokine-induced by IFN-γ (MIG) and IFN-γ inducible protein-10 (IP10) (MIG: r=0.6527, p=0.0114; IP-10: r=0.6967, p=0.0056; IP-10+MIG: r=0.7055, p=0.0048). During follow-up 30 individuals were placed on ARVs and 4 progressed to active TB. Fluctuations in SFC did not correlate with CD4 count, viral load, treatment initiation, or progression to active TB. The RD1-Elispot appears to have limited value in this setting.

Show MeSH
Related in: MedlinePlus