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Title: The pre-transplant prediction of acute cellular rejection following liver transplantation
Author: Bathgate, Andrew John
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2000
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The aim of this thesis was to investigate the effect of various parameters in patients with chronic liver disease pretransplant which may influence the occurrence of acute rejection post transplant. This may be useful in tailoring immunosuppression to avoid adverse effects in patients less likely to develop acute rejection. The role of cytokines in acute rejection is not clear but animal and human studies had suggested that tumour necrosis factor alpha (TNF-a) played some role. Polymorphisms in the genes encoding TNFa, interleukin 10 and transforming growth factor beta1 (TGFb1) which influence in vitro production of cytokines were examined in transplant patients. This showed an increase in the TNFa 2 polymorphism at position -308 in patients with acute rejection but no association with IL-10 or TGFb1 polymorphisms. Pretransplant levels of TNFa and IL-10 were measured following stimulation of peripheral blood mononuclear cells with lipopolysaccharide from patients with chronic liver disease. PBMC were preincubated with different immunosupressants. There was increased production of stimulated TNFa pretransplant in patients who went on to develop acute rejection. No relationship was found between IL-10 production and acute rejection. There were differences in the effects of tacrolimus, cyclosporin and dexamethasone on the production of both cytokines. The pretransplant immune status of patients was assessed by contact sensitisation to diphenylcyclopropenone (DPC). This demonstrated that patients unable to mount an immune response to DPC did not require treatment for acute rejection following liver transplantation. It also demonstrated a correlation between the strength of reaction to DPC and the severity of acute rejection.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available