Defining clinically pathogenic HLA-specific antibodies - granular details in characteristics in pre and early time following HLA-antibody incompatible kidney transplantation

Antibodies against donor HLA determine access to solid organ transplantation and in many cases the outcome of transplantation, but graft failure is not an inevitable consequence of their presence. Much research has been performed with two main aims – which antibodies represent the highest risk factor prior to transplantation, and second to understand how donor specific HLA antibodies behave after transplantation, with a long-term aim of being able to manipulate their production. HLA antibody incompatible kidney transplantation is the best model for examining antibody responses and this review looks at methods for interrogating the antibodies using ‘traditional’ snapshot techniques such as cytoxicity testing, and newer dissection techniques such as antibody subclass, complement binding and activity and affinity. Integral to the understanding of the large datasets generated is sophisticated mathematical analysis using techniques such as decision tree analysis and unsupervised machine learning. This review examines key aspects of this work, performed by us and others