Epstein-Barr virus in the pathogenesis of post-transpant lymphoproliferative disease

Burns, David Meriton (2015). Epstein-Barr virus in the pathogenesis of post-transpant lymphoproliferative disease. University of Birmingham. Ph.D.

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Abstract

Post-transplant lymphoproliferative disease (PTLD) is a life threatening complication of transplantation, often associated with the B-lymphotrophic Epstein-Barr virus (EBV). In order to further our understanding of the relationship between EBV infection and PTLD, a series of clinical and laboratory studies were undertaken. A multicentre United Kingdom study defined current outcomes and prognostic factors for patients with PTLD arising after solid organ transplant. A study to define incidence and risk factors for EBV reactivation and PTLD amongst patients undergoing allogeneic haematopoietic stem cell transplant (allo-HSCT) revealed greatly reduced risk amongst patients with Non-Hodgkin lymphoma previously treated with Rituximab. Complementary laboratory studies to explore the pathophysiology of EBV reactivation after allo-HSCT demonstrated that the virus maintains selectivity for, and can drive the expansion of, circulating CD27+ memory B-cells; these are normally scarce for many months after transplant. Investigations were also performed to examine the role of cell survival, DNA damage signalling and mutations as possible drivers of clonal selection in EBV-infected B-cell cultures, as an \(in\) \(vitro\) model for PTLD. Finally, work was undertaken to characterise EBV-epitope specific T-cell responses expanding in patients successfully treated with donor lymphocyte infusion for Rituximab-refractory PTLD arising after allo-HSCT.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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