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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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Related in: MedlinePlus

Schematic representation of study results.163 chronically HIV infected (ARV naïve) individuals (CD4 = 5–1142 cells/ul) were recruited in Durban, South Africa. An RD1-Elispot was performed on PBMC every 3 months for a period of 3–21 months. During the period of follow-up 30 individuals were placed on ARVs and 4 individuals progressed to active TB. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates). For 27 (21%) individuals the category is unknown due to either a lack of interpretable results (e.g. SK 179 had indeterminate Elispots at all 3 time points tested), or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions are transient or sustained.
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pone-0037920-g001: Schematic representation of study results.163 chronically HIV infected (ARV naïve) individuals (CD4 = 5–1142 cells/ul) were recruited in Durban, South Africa. An RD1-Elispot was performed on PBMC every 3 months for a period of 3–21 months. During the period of follow-up 30 individuals were placed on ARVs and 4 individuals progressed to active TB. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates). For 27 (21%) individuals the category is unknown due to either a lack of interpretable results (e.g. SK 179 had indeterminate Elispots at all 3 time points tested), or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions are transient or sustained.

Mentions: All study participants were tested by ex vivo RD1-Elispot at baseline and 3 months later. 157 individuals had subsequent blood draws every 3 months for a period of up to 21 months (Table S1). Interestingly, of the 737 Elispots displayed in the data set in Table S1, 66 (9%) indeterminate assays were reported. Of the 163 participants listed, 30 individuals were placed on ARV treatment during follow-up, 2 were placed on TB treatment, and 2 were placed on both ARV and TB treatment. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates) (Figure 1). For 27 (21%) individuals the category was unknown due to either a lack of interpretable results, or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions were transient or sustained. Figure 2 A, B, C displays examples of 4 of the main categories of Elispot kinetics.


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)

Schematic representation of study results.163 chronically HIV infected (ARV naïve) individuals (CD4 = 5–1142 cells/ul) were recruited in Durban, South Africa. An RD1-Elispot was performed on PBMC every 3 months for a period of 3–21 months. During the period of follow-up 30 individuals were placed on ARVs and 4 individuals progressed to active TB. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates). For 27 (21%) individuals the category is unknown due to either a lack of interpretable results (e.g. SK 179 had indeterminate Elispots at all 3 time points tested), or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions are transient or sustained.
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Related In: Results  -  Collection

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pone-0037920-g001: Schematic representation of study results.163 chronically HIV infected (ARV naïve) individuals (CD4 = 5–1142 cells/ul) were recruited in Durban, South Africa. An RD1-Elispot was performed on PBMC every 3 months for a period of 3–21 months. During the period of follow-up 30 individuals were placed on ARVs and 4 individuals progressed to active TB. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates). For 27 (21%) individuals the category is unknown due to either a lack of interpretable results (e.g. SK 179 had indeterminate Elispots at all 3 time points tested), or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions are transient or sustained.
Mentions: All study participants were tested by ex vivo RD1-Elispot at baseline and 3 months later. 157 individuals had subsequent blood draws every 3 months for a period of up to 21 months (Table S1). Interestingly, of the 737 Elispots displayed in the data set in Table S1, 66 (9%) indeterminate assays were reported. Of the 163 participants listed, 30 individuals were placed on ARV treatment during follow-up, 2 were placed on TB treatment, and 2 were placed on both ARV and TB treatment. Of the 129 individuals who were not placed on ARVs or TB treatment during follow-up, 5 categories of Elispot kinetics were observed: 45 (35%) individuals were consistently negative at each time-point tested, 22 (17%) individuals were consistently positive at each time-point tested, 8 (6%) individuals displayed sustained conversions (three or more positive Elispots after at least one negative Elispot), 11 (9%) individuals displayed transient conversions (one or two positive Elispots between negative plates), and 16 (12%) individuals displayed transient reversions (one or two negative Elispots between positive plates) (Figure 1). For 27 (21%) individuals the category was unknown due to either a lack of interpretable results, or the absence of either pre-baseline samples or further follow-up to determine if observed reversions and conversions were transient or sustained. Figure 2 A, B, C displays examples of 4 of the main categories of Elispot kinetics.

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