Department of Physiological Sciences
Permanent URI for this community
Browse
Browsing Department of Physiological Sciences by browse.metadata.advisor "Glashoff, Richard"
Now showing 1 - 1 of 1
Results Per Page
Sort Options
- ItemImmune activation in HIV-positive patients on combined anti-retroviral treatment (cART) as a high risk group for the development of cardiovascular diseases(Stellenbosch : Stellenbosch University, 2017-12) Teer, Eman Aboajla; Essop, M. Faadiel; Glashoff, Richard; Stellenbosch University. Faculty of Science. Dept. of Physiological Sciences.ENGLISH ABSTRACT: Although roll-out of combined anti-retroviral treatment (cART) has blunted HIV-AIDS onset, studies show increased development of cardio-metabolic complications in HIV-infected individuals. For this study we hypothesized that HIV-induced low-grade inflammation perturbs immune cell function/activation, thereby contributing to an increased risk for cardiovascular diseases (CVD) onset. Here we aimed to identify changes in monocyte and T cell subsets and determine its relationship to: (a) classical markers of HIV progression (CD4 count, viral load); (b) immune activation status; (c) endothelial dysfunction; and (d) traditional lipid profile and subclasses. Eighty participants were recruited from the Worcester Community Day Center (Worcester, Western Cape, South Africa): n=13 HIV-negative, n=67 HIV-positive. Recruits were divided as HIV-naïve and HIV-treated (on cART), and also groups based on CD4 count (control group, HIV-positive with CD4count > 500 cells/µL, CD4 count from 200–500 cells/µL and CD4 count < 200 cells/µL). Clinical histories and a validated lifestyle questionnaire were completed. Fasted blood was collected and used to assess monocyte subpopulation phenotype (non-classical, intermediate, classical) by flow cytometry together with tissue factor (a marker for thrombus formation) and CD38 (a marker for immune activation) expression on monocyte and T cell subsets (CD4, CD8). Classical regulatory T cells (CD4+CD25++FOXP3+) with activation markers (glycoprotein A repetitions predominant [GARP] and special AT-rich sequence binding protein 1 [SATB-1]) were also evaluated together with an assessment of endothelial function (flow-mediated dilatation). C-reactive protein levels together with the traditional lipid profile were also evaluated. In addition, an assessment of high-density lipoprotein (HDL) and low-density lipoprotein (LDL) subclasses was also completed. Our data revealed a robust increase in inflammation/immune activation and coagulation markers on CD8+ and CD4+ T cell populations, respectively (CD8+CD142+ [P = 0.01] and CD4+CD142+ [P = 0.0003]). Increased co-expression of inflammation and coagulation markers were also observed on both CD8+ and CD4+ T cells (CD8+142+CD38+ [P = 0.0001] and CD4+142+38+ [< 0.0001]). In addition, we found an expansion of both non-classical (P = 0.0001) and intermediate monocytes (P = 0.05) that were highly correlated with immune activation, coagulation and HIV disease progression markers. There was also an expansion of CD4+FOXP3+ regulatory T cells (P = 0.0005), together with higher levels of GARP (P = 0.001) and SATB-1 (P = 0.04) (especially in patients with relatively low CD4 counts). The lipid profile data revealed interesting changes, i.e. a significant decrease during early HIV-infection but with substantial increase after cART initiation. In addition, we also found significant changes in HDL and LDL subclasses. The most novel findings of this study are: a) the identification of a unique coagulation marker (CD142) expressed on CD8 and CD4 T cells and its relatively early expression in HIV-infected individuals (treatment naïve). CD142 is also co-expressed with immune activation and strongly correlates with disease progression markers; b) changes in lipid subclasses that significantly correlate to HIV immunological markers despite a decrease in terms of the traditional lipid profile expected. Such subclass changes may also be a driver for CVD onset, although further research is needed to pursue this question; and c) upregulation of both antiinflammatory GARP and pro-inflammatory SATB-1 in regulatory T cells in HIV-treated individuals (with immune dysregulation) altering regulatory T cell function and also potentially contributing to CVD onset. Thus we propose that clinicians could be aware of immune activation and coagulation with HIV infection (even at relatively early stages of disease progression) as monitoring and control of these factors could result in improved healthcare and the long-term well-being for such patients.