Lack of good correlation of serum CC-chemokine levels with human immunodeficiency virus-1 disease stage and response to treatment

Ye, Ping; Kazanjian, Powel; Kunkel, Steven L.; Kirschner, Denise E.

doi:10.1016/j.lab.2004.01.012

Cited by 13 publications

(14 citation statements)

References 51 publications

(66 reference statements)

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“…Ye Ping et al demonstrated that there were no significant differences among the four clinical stages of HIV-1 infection in the serum levels of CC-chemokines [47] and we also observed no significant differences among the two groups of patients with CD4 + T cell between 200-400 cells/μL and CD4 + T cell> 400 cells/μL for MIP-3α. The weakness of our study is that the levels of MIP-3α have not been explored and measured in the fluid at the recto-colonel level.…”

Section: Discussionsupporting

confidence: 62%

Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

et al. 2016

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Objective Uncontrolled HIV infection progresses to the depletion of systemic and mucosal CD4 and AIDS. Early HIV infection may be associated with increases in the concentration of MIP-3α in the blood and gut fluids. MIP-3α/CCL20 is the only chemokine known to interact with CCR6 receptors which are expressed on immature dendritic cells and both effector and memory CD8+ and CD4+ T cells. The role and prognostic value of blood levels of MIP-3α in HIV-infected individuals has yet to be described. Methods We determined the serum levels of MIP-3α, and IFN-γ, in 167 HIV-1-infected and 27 HIV-1-uninfected men participating in the Multicenter AIDS Cohort Study (MACS). The blood biomarkers were measured using enzyme-linked immunosorbent assays (ELISA) and the cell phenotypes using flow cytometry. Results Median serum levels of MIP-3α in HIV-1-infected and uninfected men was significantly different (p<0.0001) and were 21.3 pg/mL and 6.4 pg/mL respectively. The HIV-1-infected men with CD4+ T cell count <200 cells/μL showed the highest median serum MIP-3α (23.1 pg/mL). Serum levels of MIP-3α in HIV-1 infected (n=167) were negatively correlated with absolute number of CD4+ T cell (p=0.01) and were positively correlated with CD38 molecules on CD8+ T cells (p=0.0002) and with serum levels of IFN-γ (0.006). Conclusion Serum levels of MIP-3α concomitantly increase with plasma levels of IFN-γ, CD38 expression on CD8+ T cells, and decreased of absolute CD4+ T cells in HIV-1-infected men. A higher blood level of MIP-3α may be representation of locally high level of MIP-3α and more recruitment of immature dendritic cell at site of infection. Involvement of CCR6/CCL20 axis and epithelial cells at the recto-colonel level may enhance sexual transmission of HIV-1 in MSM and may be useful as a prognostic marker in HIV-1-infection and AIDS.

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Section: Discussionsupporting

confidence: 62%

Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

et al. 2016

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“…[33][34][35] This raises the possibility that the higher serum levels of MIP-1a in obese individuals could affect HIV-1 entry or replication in peripheral CD4 + T cells, but current published data on the relationship between serum MIP-1a and HIV replication or the response to ART are conflicting. [36][37][38] We hypothesize that the increased circulating MIP-1a derives from adipose deposits, but further studies are needed to determine whether higher serum levels affect the HIV disease state or are simply a reflection of excess adiposity.…”

Section: Koethe Et Almentioning

confidence: 99%

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Koethe

Dee

Bian

et al. 2013

AIDS Research and Human Retroviruses

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Obesity and chronic, treated HIV infection are both associated with persistent systemic inflammation and a similar constellation of metabolic and cardiovascular diseases, but the combined effects of excess adiposity and HIV on circulating proinflammatory cytokines and other biomarkers previously shown to predict disease risk is not well described. We measured inflammation biomarker levels in 158 predominantly virologically suppressed adults on long-term antiretroviral therapy (ART) with a range of body mass index (BMI) values from normal to morbidly obese. We assessed the relationship between BMI and each biomarker using multivariable linear regression adjusted for age, sex, race, CD4+ count, tobacco use, data source, protease inhibitor use, and routine nonsteroidal antiinflammatory drug (NSAID) or aspirin use. Among normal-weight (n = 48) and overweight participants (n = 41; BMI < 30 kg/m 2 ), incremental BMI increases were associated with significantly higher serum highly sensitive C-reactive protein (hsCRP; b = 2.47, p = 0.02) and tumor necrosis factor (TNF)-a receptor 1 levels (b = 1.53, p = 0.03), and significantly lower CD14 levels (b = 0.84, p = 0.01), but similar associations were not observed in the obese participants. Among the obese (n = 69; BMI ‡ 30 kg/m 2 ), however, higher serum levels of interleukin-6 (IL-6; b = 1.30, p = 0.02) and macrophage inflammatory protein-1a (b = 1.77, p < 0.01) were associated with higher BMI, a finding not observed among the nonobese. Among all participants, IL-6 and TNF-a receptor 1 levels were most closely associated with hsCRP ( p < 0.01). Further studies are needed to determine whether higher serum inflammation biomarker levels found in obese HIV-infected individuals on ART reflect an increased likelihood of adverse health outcomes, or if novel markers to estimate mortality and disease risk are needed in this population.

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“…However, there is a cautionary note: the biomarker potential of CCR5 ligands requires consideration of the fact that although antiviral immunity is afforded by release of HIV-suppressive CCR5 ligands from activated leukocytes, serum levels of these biomarkers may correlate poorly with HIV-AIDS outcomes [114] and high levels of chemokines by imparting pro-inflammatory effects [115] may accelerate disease progression.…”

Section: Mendelian Randomization and Hiv-associated Outcomes: Case Stmentioning

confidence: 99%

Mendelian randomization: potential use of genetics to enable causal inferences regarding HIV-associated biomarkers and outcomes

Castiblanco

Walter³

et al. 2010

Current Opinion in HIV and AIDS

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Purpose of review It is unknown whether biomarkers simply correlate with or are causal for HIV-associated outcomes. Mendelian randomization (MR), is a genetic epidemiologic approach used to disentangle causation from association. Here, we discuss the potential use of MR for differentiating whether biomarkers are correlating with or causal for HIV-associated outcomes. Recent findings MR refers to the random allocation of alleles at the time of gamete formation. In observational epidemiology, this refers to the use of genetic variants to estimate a causal effect between a modifiable risk factor and an outcome of interest. A formal MR study using a genetic marker as a proxy for the biomarker has not been conducted in the HIV field. However, in the post-genomic era this approach is being used increasingly. Examples are evidence for the causal role of body mass index on blood pressure and non-causal role of CRP in coronary heart disease. We discuss the conceptual framework, uses and limitations of MR in the context of HIV infection as well as specific biomarkers (IL-6, CRP) and genetic determinants (e.g., in CCR5, chemokine, and DARC genes) that associate with HIV-related outcomes. Summary Making the distinction between correlation and causality has particular relevance when a biomarker (e.g. IL-6) is potentially modifiable, in which case a biomarker-guided targeted treatment strategy may be feasible. Although the tenets of MR rest on strong assumptions, and conducting an MR study in HIV infection presents many challenges, it may offer the potential to identify causal biomarkers for HIV-associated outcomes.

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Lack of good correlation of serum CC-chemokine levels with human immunodeficiency virus-1 disease stage and response to treatment

Cited by 13 publications

References 51 publications

Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

Macrophage Inflammatory Protein-3 Alpha (MIP-3α)/CCL20 in HIV-1- Infected Individuals

Circulating Interleukin-6, Soluble CD14, and Other Inflammation Biomarker Levels Differ Between Obese and Nonobese HIV-Infected Adults on Antiretroviral Therapy

Mendelian randomization: potential use of genetics to enable causal inferences regarding HIV-associated biomarkers and outcomes

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