Post-transplantation antibody monitoring and HLA antibody epitope identification

We earlier reviewed the reasons to believe that HLA antibodies are the cause of chronic rejection. In this review we shall focus on two questions: first, why is it important to test transplant recipients for alloantibody post-transplantation? Recent large-scale prospective studies on the effect of alloantibodies on graft survival showed that rates of graft failure more than doubled in recipients who had alloantibodies compared with antibody-free patients. The causal relationship between alloantibody and transplant rejection — especially chronic rejection — has been demonstrated both experimentally and clinically. We recommend universal testing of allograft recipients for antibodies since that will help clinicians identify this obvious risk factor and take appropriate action to minimize deterioration of transplant function. Second, why is it important to identify HLA antibody epitopes? Since HLA antibody is a potential cause of graft rejection, identifying the epitope — or antigenic determinant — to which an antibody binds, becomes very important. Such identification lets clinicians target the real transplant antigen and may lay a foundation for the development of new treatments and/or new matching strategies to reduce the occurrence of antibody-mediated rejection (AMR). Now that natural HLA antibodies have been identified; it is important to distinguish these from donor-specific epitopes. The establishment of 103 HLA class I epitopes, 83 class II, and 7 major-histocompatibility-complex class I-related chain A (MICA) epitopes is reviewed. Single antigen bead technology has been important in identifying the epitopes by experiment.