Anti-idiotypic antibodies in human leukocyte antigen (HLA) antibody-incompatible renal transplantation

The production of antibodies against Human Leukocyte Antigen (HLA) is called sensitisation and can occur through transfusion, pregnancy or transplantation. As the presence of antibodies against donor HLA can result in a high risk of antibody mediated rejection, highly sensitised patients are limited to a restricted pool of possible donors. HLA antibody incompatible (HLAi) transplants can be performed to enable renal transplantation although outcomes are inferior to antibody compatible transplantation and therefore improvements to this process are required. Interestingly, several studies from the 1980s and 1990s reported the presence of anti-idiotypic antibodies against HLA antibodies in transplanted patients. These antibodies are specific to the antigen binding site of HLA antibodies, providing self-regulation of the immune response. As knowledge about whether an individual has previously produced anti-idiotypic antibodies could help to inform decisions about the risks of proceeding with a transplant, this project aimed to determine whether anti-idiotypic antibodies are present in the serum of patients following HLAi renal transplantation. To enable this to be investigated, a method was developed to deplete donor specific HLA-A2 antibodies from patient samples, retaining any anti-idiotypic antibodies. This depleted serum was then incubated with the original serum to determine whether it could inhibit detection of donor-specific antibodies. The data from this project showed a modest reduction in donor-specific antibody, indicating that anti-idiotypic antibodies may be present. To develop this project, further repeats are required and methods which directly demonstrate the presence of anti-idiotypic antibodies should be investigated.