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Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease.

Seu L, Ortiz GM, Burt TD, Deeks SG, Martin JN, McCune JM - AIDS Res Ther (2014)

Bottom Line: We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART.This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL].Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.

ABSTRACT
The level (or frequency) of circulating monocyte subpopulations such as classical (CD14(hi)CD16(-)) and non-classical (CD14(dim)CD16(+)) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14(hi)CD16(-)) and decreased levels of non-classical monocyte populations (CD14(dim)CD16(+)). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14(+) monocytes were significantly associated with the degree of CD4(+) T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4(+) T cell recovery after the initiation of ART.

No MeSH data available.


Related in: MedlinePlus

Antiretroviral therapy is associated with decreased PBMC mRNA levels of HMOX1. (A) Cross-sectional analysis of the relative transcript expression levels of HMOX1/HPRT in patients described in Table 1. Column statistics were performed by 1-way ANOVA. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (B) Longitudinal changes in relative transcript expression levels of HO-1/HPRT were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre-ART suppressed subjects" described in Table 2). Student’s paired t-test was performed with p value = 0.05.
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Figure 3: Antiretroviral therapy is associated with decreased PBMC mRNA levels of HMOX1. (A) Cross-sectional analysis of the relative transcript expression levels of HMOX1/HPRT in patients described in Table 1. Column statistics were performed by 1-way ANOVA. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (B) Longitudinal changes in relative transcript expression levels of HO-1/HPRT were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre-ART suppressed subjects" described in Table 2). Student’s paired t-test was performed with p value = 0.05.

Mentions: Relative transcript levels of HO-1 were assessed from thawed PBMCs from untreated viral controllers, untreated viremic subjects, ART-treated subjects, and HIV-seronegative subjects (Table 1). There were no statistically significant differences in the levels of HO-1 transcript across all patient groups (Figure 3A).


Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4(+) T cell recovery after the initiation of antiretroviral therapy for HIV disease.

Seu L, Ortiz GM, Burt TD, Deeks SG, Martin JN, McCune JM - AIDS Res Ther (2014)

Antiretroviral therapy is associated with decreased PBMC mRNA levels of HMOX1. (A) Cross-sectional analysis of the relative transcript expression levels of HMOX1/HPRT in patients described in Table 1. Column statistics were performed by 1-way ANOVA. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (B) Longitudinal changes in relative transcript expression levels of HO-1/HPRT were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre-ART suppressed subjects" described in Table 2). Student’s paired t-test was performed with p value = 0.05.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4150425&req=5

Figure 3: Antiretroviral therapy is associated with decreased PBMC mRNA levels of HMOX1. (A) Cross-sectional analysis of the relative transcript expression levels of HMOX1/HPRT in patients described in Table 1. Column statistics were performed by 1-way ANOVA. Statistical significance is denoted as *p < 0.05, **p < 0.01, and ***p < 0.001. (B) Longitudinal changes in relative transcript expression levels of HO-1/HPRT were measured during pre-ART to post-ART time points from thawed PBMCs of ART-treated subjects (see "pre-ART suppressed subjects" described in Table 2). Student’s paired t-test was performed with p value = 0.05.
Mentions: Relative transcript levels of HO-1 were assessed from thawed PBMCs from untreated viral controllers, untreated viremic subjects, ART-treated subjects, and HIV-seronegative subjects (Table 1). There were no statistically significant differences in the levels of HO-1 transcript across all patient groups (Figure 3A).

Bottom Line: We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART.This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL].Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94110, USA ; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 94110, USA.

ABSTRACT
The level (or frequency) of circulating monocyte subpopulations such as classical (CD14(hi)CD16(-)) and non-classical (CD14(dim)CD16(+)) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4(+) T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of <1000 copies/mL], untreated virologic non-controllers [VL > 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4(+) T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14(hi)CD16(-)) and decreased levels of non-classical monocyte populations (CD14(dim)CD16(+)). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14(+) monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14(+) monocytes were significantly associated with the degree of CD4(+) T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4(+) T cell recovery after the initiation of ART.

No MeSH data available.


Related in: MedlinePlus