Dataset Information

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

ABSTRACT: The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF receptor type 2 (TNFR-2), and plasma microparticles--during the earliest stages of infection following HIV type 1 (HIV-1) transmission in plasma samples from U.S. plasma donors. Significant plasma TRAIL level elevations occurred a mean of 7.2 days before the peak of plasma viral load (VL), while TNFR-2, Fas ligand, and microparticle level elevations occurred concurrently with maximum VL. Microparticles had been previously shown to mediate immunosuppressive effects on T cells and macrophages. We found that T-cell apoptotic microparticles also potently suppressed in vitro immunoglobulin G (IgG) and IgA antibody production by memory B cells. Thus, release of TRAIL during the onset of plasma viremia (i.e., the eclipse phase) in HIV-1 transmission may initiate or amplify early HIV-1-induced cell death. The window of opportunity for a HIV-1 vaccine is from the time of HIV-1 transmission until establishment of the latently infected CD4(+) T cells. Release of products of cell death and subsequent immunosuppression following HIV-1 transmission could potentially narrow the window of opportunity during which a vaccine is able to extinguish HIV-1 infection and could place severe constraints on the amount of time available for the immune system to respond to the transmitted virus.

SUBMITTER: Gasper-Smith N

PROVIDER: S-EPMC2493338 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

Gasper-Smith Nancy N Crossman Deanna M DM Whitesides John F JF Mensali Nadia N Ottinger Janet S JS Plonk Steven G SG Moody M Anthony MA Ferrari Guido G Weinhold Kent J KJ Miller Sara E SE Reich Charles F CF Qin Li L Self Stephen G SG Shaw George M GM Denny Thomas N TN Jones Laura E LE Pisetsky David S DS Haynes Barton F BF

Journal of virology 20080528 15

The death of CD4(+) CCR5(+) T cells is a hallmark of human immunodeficiency virus (HIV) infection. We studied the plasma levels of cell death mediators and products--tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), Fas ligand, TNF receptor type 2 (TNFR-2), and plasma microparticles--during the earliest stages of infection following HIV type 1 (HIV-1) transmission in plasma samples from U.S. plasma donors. Significant plasma TRAIL level elevations occurred a mean of 7.2 days ...[more]

PMID: 18508902

Similar Datasets

Project description:Study designMeta-analysis to collect all the relevant studies to further investigate whether or not the FAS ligand (FASL) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) genetic polymorphisms are associated with susceptibility to intervertebral disc degeneration (IDD) in Chinese Han population.ObjectiveTo investigate whether or not the FASL and TRAIL genetic polymorphisms are associated with susceptibility to IDD in Chinese Han population.Summary of background dataFASL and TRAIL are both apoptotic gene. Several studies have assessed the associations of FASL and TRAIL gene with risk of IDD in Chinese Han population, but the results are inconsistent.MethodsWe systematically searched the PubMed, EMBASE, Medline, Scopus, Web of Science, CBM, and the Cochrane Library databases. Eligible studies assessing the polymorphisms in the FASL and TRAIL gene and risk of IDD were incorporated. The pooled odds ratio (OR) with its 95% confidence intervals (95% CI) was used.ResultsSix studies with a total of 1766 IDD cases and 1533 controls were finally included in the meta-analysis. Meta-analysis of FASL-844C/T (rs763110) polymorphism was statistically associated with decreased IDD risk under all genetic models (allele model: OR = 0.68, 95% CI 0.59-0.80, P = 0.000; homozygote model: OR = 0.35, 95% CI 0.25-0.53, P = 0.000; dominant model: OR = 0.38, 95% CI 0.25-0.58, P = 0.000; recessive model: OR = 0.69, 95% CI 0.58-0.84, P = 0.000). There was a significant association between TRAIL-1595C/T (rs1131580) polymorphism with increased IDD risk under each genetic model (allele model: OR = 1.77, 95% CI 1.47-2.13, P = 0.000; homozygote model: OR = 2.44, 95% CI 1.70-3.51, P = 0.000; dominant model: OR = 1.67, 95% CI 1.22-2.29, P = 0.002; recessive model: OR = 3.13, 95% CI 2.40-4.08, P = 0.000). In addition, the association between TRAIL-1525G/A (rs1131568) polymorphism and the susceptibility of IDD was statistically significant under all genetic models.ConclusionThe present meta-analysis demonstrated that FASL and TRAIL polymorphisms were significantly associated with susceptibility to IDD in Chinese Han population.Level of evidence1.

Project description:Aims/hypothesisHigher plasma concentrations of tumour necrosis factor receptor (TNFR)-1, TNFR-2 and kidney injury molecule-1 (KIM-1) have been found to be associated with higher risk of kidney failure in individuals with type 2 diabetes in previous studies. Whether drugs can reduce these biomarkers is not well established. We measured these biomarkers in samples of the CANVAS study and examined the effect of the sodium-glucose cotransporter 2 inhibitor canagliflozin on these biomarkers and assessed whether the early change in these biomarkers predict cardiovascular and kidney outcomes in individuals with type 2 diabetes in the CANagliflozin cardioVascular Assessment Study (CANVAS).MethodsBiomarkers were measured with immunoassays (proprietary multiplex assay performed by RenalytixAI, New York, NY, USA) at baseline and years 1, 3 and 6. Mixed-effects models for repeated measures assessed the effect of canagliflozin vs placebo on the biomarkers. Associations of baseline levels and the early change (baseline to year 1) for each biomarker with the kidney outcome were assessed using multivariable-adjusted Cox regression.ResultsIn total, 3523/4330 (81.4%) of the CANVAS participants had available samples at baseline. Each doubling in baseline TNFR-1, TNFR-2 and KIM-1 was associated with a higher risk of kidney outcomes, with corresponding HRs of 3.7 (95% CI 2.3, 6.1; p < 0.01), 2.7 (95% CI 2.0, 3.6; p < 0.01) and 1.5 (95% CI 1.2, 1.8; p < 0.01), respectively. Canagliflozin reduced the level of the plasma biomarkers with differences in TNFR-1, TNFR-2 and KIM-1 between canagliflozin and placebo during follow-up of 2.8% (95% CI 3.4%, 1.3%; p < 0.01), 1.9% (95% CI 3.5%, 0.2%; p = 0.03) and 26.7% (95% CI 30.7%, 22.7%; p < 0.01), respectively. Within the canagliflozin treatment group, each 10% reduction in TNFR-1 and TNFR-2 at year 1 was associated with a lower risk of the kidney outcome (HR 0.8 [95% CI 0.7, 1.0; p = 0.02] and 0.9 [95% CI 0.9, 1.0; p < 0.01] respectively), independent of other patient characteristics. The baseline and 1 year change in biomarkers did not associate with cardiovascular or heart failure outcomes.Conclusions/interpretationCanagliflozin decreased KIM-1 and modestly reduced TNFR-1 and TNFR-2 compared with placebo in individuals with type 2 diabetes in CANVAS. Early decreases in TNFR-1 and TNFR-2 during canagliflozin treatment were independently associated with a lower risk of kidney disease progression, suggesting that TNFR-1 and TNFR-2 have the potential to be pharmacodynamic markers of response to canagliflozin.

Dataset Information

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

Publications

Induction of plasma (TRAIL), TNFR-2, Fas ligand, and plasma microparticles after human immunodeficiency virus type 1 (HIV-1) transmission: implications for HIV-1 vaccine design.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets