HLA Epitope Matching in Kidney Transplantation: An Overview for the General Nephrologist

Abstract

Rapid changes in tissue-typing technology, including the widespread availability of highly specific molecular typing methods and solid-phase assays for the detection of allele-specific anti-HLA antibodies, make it increasingly challenging to remain up to date with developments in organ matching. Terms such as epitopes and eplets abound in the transplantation literature, but often it can be difficult to see what they might mean for the patient awaiting transplantation. In this review, we provide the historical context for current practice in tissue typing and explore the potential role of HLA epitopes in kidney transplantation. Despite impressive gains in preventing and managing T-cell-mediated rejection and the associated improvements in graft survival, the challenge of the humoral alloresponse remains largely unmet and is the major cause of late graft loss. Describing HLA antigens as a series of antibody targets, or epitopes, rather than based on broad seroreactivity patterns or precise amino acid sequences may provide a more practical and clinically relevant system to help avoid antibody-mediated rejection, reduce sensitization, and select the most appropriate organs in the setting of pre-existing alloantibodies. We explain the systems proposed to define HLA epitopes, summarize the evidence to date for their role in transplantation, and explore the potential benefits of incorporating HLA epitopes into clinical practice as this field continues to evolve toward everyday practice.

Keywords: Human leukocyte antigen (HLA); antibody-mediated rejection (AMR); epitope; epitope matching; eplet; graft loss; graft survival; histocompatibility; kidney transplant; kidney transplantation; matching; molecular typing.