Cytokine immune regulation in cytomegalovirus-infected kidney transplant patients

Latif, Farah 2024. Cytokine immune regulation in cytomegalovirus-infected kidney transplant patients. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Kidney transplantation is the optimal management option of end-stage kidney disease. Despite advances in transplantation, infectious complications post-transplantation remain a significant problem. Human cytomegalovirus (CMV) is a highly prevalent virus, establishing life-long viral infection in the human host. Whilst immunocompetent individuals can control CMV viral load, immunocompromised kidney transplant recipients, particularly those that are CMV naïve (R-) that receive a kidney from a seropositive donor (D+), can experience a severe illness from CMV infection. Current CMV infection risk stratification and surveillance strategies are limited. This thesis revealed that cytokine and immune cellular gene expression signatures following kidney transplantation are directly affected by CMV exposure and infection. Thus, cytokines and associated cellular immune responses can help us predict CMV infection occurrence and outcome. Plasma FLT3L is a novel marker of subsequent CMV infection occurrence and efficiency of viral control in CMV naïve individuals who receive a kidney from a seropositive donor. Thus, plasma FLT3L concentration could be used to aid risk stratification of these patients. FLT3L was expressed primarily by T cells, with particular upregulation of FLT3L by CD4+ and CD8+ ab T cells, and its expression was elevated by CMV exposure despite no clinically detectable anti-CMV IgG in the majority of these patients at this time. Furthermore, I observed that CMV infected patients had an increase in their urinary MCP-1 concentration in comparison to D+/R- patients that did not develop viraemia. Our emerging data suggest that elevated urine MCP-1 concentration, may correlate with a drop in graft function, 1- year post-kidney transplant, following CMV infection. CD14+ and CD16+ cells were elevated in viraemic patients, indicating that higher MCP-1 concentration measured in these individuals may be a consequence of elevated monocytic responses in the circulation and may broadly promote inflammatory cytokine responses in these patients.

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Medicine
Date of First Compliant Deposit:	27 May 2025
Last Modified:	27 May 2025 11:07
URI:	https://orca.cardiff.ac.uk/id/eprint/178524

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