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Title: Indirect effects of cytomegalovirus in kidney transplantation
Author: Shabir, Shazia
ISNI:       0000 0004 6494 6524
Awarding Body: University of Birmingham
Current Institution: University of Birmingham
Date of Award: 2017
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Cytomegalovirus (CMV) infection is the most frequent and significant opportunistic infection in kidney transplant recipients. It is associated with direct (CMV disease) and indirect (rejection, poor graft survival) effects with resultant increases in morbidity and mortality. The mechanisms responsible for the indirect effects of CMV infection remain unclear. In this thesis, the indirect effects of cytomegalovirus infection in kidney transplantation are studied. Firstly, the mechanism of CMV infection is investigated. Secondly, the mechanism of CMV associated kidney transplant damage is explored. Thirdly, an assessment for the role of CMV in causing immunosenescence within the kidney transplantation cohort is undertaken. This thesis provides previously undescribed and direct evidence of immune hypo- responsiveness to latent CMV. I have shown CD4⁺CD27⁻CD28^null cells are pathognomonic of prior CMV exposure and have a role in glomerular endothelial cell damage, an effect which may be mediated by NKG2D. Higher CD4⁺CD27⁻CD28^null cell counts at 12 months post-transplantation predict a steeper decline in kidney allograft function thereafter. I provide novel insight into the ‘indirect’ effect of CMV in the pathogenesis of CD8⁺CD28^null cells. My study is the first to demonstrate a temporal association between elevated CD8⁺CD28^null cell frequencies and subsequent development of clinically relevant episodes of infection. The findings from this thesis set the scene for future interventional research and therapeutic strategies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QR180 Immunology ; RB Pathology