Bastiaansen, M.A.J. (2017) T cell phenotype in end-stage renal disease patients. thesis, Medicine.
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Abstract
End-stage renal disease (ESRD) is a major health problem and associated with significant morbidity and increased mortality, due to a higher risk of infections and cardiovascular diseases. The high levels of uremic toxins lead to the dysregulation of the immune system, in which T lymphocytes play a central role. Before starting with a big cohort, a pilot study is needed to optimizing the protocol and looking to differences in T lymphocytes between healthy controls and dialysis patients. We looking to four different subtypes of T lymphocytes: exhaustive, regulatory, cytotoxic and memory T cells. To determine the T cell function, this study looked into the differences in the cytokine production between dialysis patients and healty controles. Blood from three patients and three healthy controls was obtained and analyzed with flow cytometry, after peripheral blood mononuclear cell (PBMC) isolation. In this technique, isolated PBMCs are subsequently stained with antibodies bound to a flurochrome, allowing measurements of the expression of different surface and intracellular markers. With the extracted data, the subsets of T lymphocytes could be characterized and differences between the healthy control and the ESRD patients were determined. This pilot study gave insight in the status of various T cell phenotypes in ESRD patients. The results show a lower amount of regulatory T cells in ESRD patients. Additionally, an upregulation of exhaustive T cell markers was found in dialysis patients, in particular the PD-1 expression. Furthermore, this study demonstrates that ESRD patients express an increased amount of IL-2, IL-17 and in particular IFN-γ, where the biggest differences relative to the control group were found. The data suggest higher amounts of cytotoxic CD4 cells in the kidney patients; these cells are characterized by a low CD28 expression, which results in an expansion of the granzyme-B secretion. Finally, based on our findings it can be concluded that the T memory cells of patients with ESRD are dysregulated, with a reduced amount of naïve T cells and increased effector memory cells. This pilot study is important and essential before starting with a large cohort. We optimized the 4-panel flow cytometry experiment and now we are able to start with our larger study hopefully confirm the differences in T lymphocytes between healthy controls and dialysis patients.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisor Groningen and The Netherlands/GIPS-M: and Son, Prof. dr. W.J. van and Department of Internal Medicine University Medical Center Gr |
| Supervisor name: | Riella L.V. MD PhD and Assistant Professor of Medicine at Harvard Medical School and Associate Medical Director of Kidney and Pancreas Transplant |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:44 |
| Last Modified: | 25 Jun 2020 10:44 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/574 |
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