| Popis: |
Cardiac transplantation continues to be the main treatment pathway for end stage heart failure. The process holds many challenges for the recipients' immune system. Modern immunosuppression has improved survival to one year greatly, but the main limitation to survival following this remains chronic rejection, taking the form of coronary artery vasculopathy (CA V). Recent studies have found strong associations with antibody mediated rejection and CA V. This study investigates the role of antibody mediated rejection (AMR), and the complement system, within cardiac transplantation and it involvement with the development of CAV. Here, the presence of complement components was demonstrated within cardiac tissues taken through the transplant process and up regulated following brain death, through ischaemia and reperfusion of the graft. The deposition of complement within the first two years post transplantation was retrospectively associated with the future development of CA V. However, the deposition of complement alone did not reflect the occurrence of clinical AMR episodes. Antibodies within the tissues were also observed, with serum studies confirming the presence of auto reactive anti vimentin IgM, within the recipients. Developing the study further to investigate the CA V lesion, complement components and antibodies were co-localised to smooth muscle cells within the lesion. These data have led to the conclusion that antibody and complement deposition have a pivotal role in the cause and progression of CA V. Investigations into the source of the anti graft antibody, led to a six month post operative survey ofB cell population in cardiac recipients, leading to description of an altered B cell population within an immunosuppressed environment, with expansion in a little known CD21 10w B cell phenotype. |
