| Summary: | Since the 1980's cardiac transplantation has become accepted management of end-stage cardiac failure in all ages. Practice has evolved with newer strategies in paediatrics including the use of ABO-incompatible donors and increasingly the recognition of the importance of antibodies to human leukocyte antigens (HLA). Transplantation cannot be regarded as a cure and there are ongoing risks including rejection, coronary artery disease and death. There is increasing interest in outcomes of ABO-incompatible transplantation and the impact of higher pre-transplant isohaemagglutinin titres in the recipients of these grafts. In a related area, it has recently been recognised that development of de novo HLA antibodies following transplant may have an impact on long term outcomes and survival but data in this area has mainly been focused on the kidney transplant population and there are very few studies in paediatric cardiac patients. This thesis is an investigation into antibody development following paediatric cardiac transplantation and through two separate but related studies looks at the incidence and impact of de novo HLA antibodies, and outcomes including isohaemagglutinin development following ABO-incompatible cardiac transplantation. Through testing of stored samples taken over 15 years in a cohort of patients, the first part of this thesis shows that the incidence of donor-specific HLA antibodies (DSA) is higher than originally thought, but appears to only have a significant effect on outcomes if they are persistent, particularly Class 11antibodies. This is the first study to demonstrate this in children. The second part of this thesis provides data on outcomes following ABO-incompatible transplantation with focus on patients with higher pretransplant isohaemagglutinins, demonstrating increased early rejection in this group but good longer-term outcomes. This provides valuable data for both of these patient groups and a basis for clinical decision making in the management of patients found to have new onset DSA.
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