Towards precision medicine in kidney transplantation: Epitope based HLA-matching and improved DSA diagnostics

Refinement of immunological pre-transplant risk assessment, specifically by improving the molecular compatibility between donor and recipient and by enhancing the characterization of the recipient’s pre-established immunological memory, is key to transit to an improved organ allocation and a personalized immunosuppression in solid organ transplantation (SOT). For both of these diagnostic clarifications, novel conceptual and technological achievements have been attained, but still need to be perfected. This doctoral thesis is dedicated to both topics. Publication 1 presents a study on the immunogenicity of human leukocyte antigen (HLA) epitopes, the results and insights of which contribute to better prediction of newly formed (de novo) immune responses in allograft recipients. The study presented in Publication 2 addresses the question of which pre-transplant donor specific HLA antibodies (DSA) are clinically relevant and why. The results demonstrate how different antibody-IgG compositions affect complement activation, the most detrimental antibody effector function in relation to antibody-mediated rejection (AMR). Finally, Publication 3 reviews relevant issues in the context of DSA characterization by the Single Antigen Bead (SAB) assay, which has become the central assay for HLA-antibody characterization in transplant diagnostics.