Results and reflections from the PROfiling Consortium on Antibody Repertoire and Effector functions in kidney transplantation: A mini-review

Kidney transplantation is the best treatment option for patients with end-stage renal disease (ESRD). The waiting time for a deceased donor kidney in the Netherlands is approximately 3 years. Mortality among patients on the waiting list is high. The aim of the PROCARE consortium (PROfiling Consortium on Antibody Repertoire and Effector functions) was to decrease the waiting time by providing a matching algorithm yielding a prolonged graft survival and less HLA-immunization compared with the currently used Eurotransplant Kidney allocation system. In this study, 6097 kidney transplants carried out between January 1995 and December 2005 were re-examined with modern laboratory techniques and insights that were not available during that time period. In this way, we could identify potential new parameters that can be used to improve the matching algorithm and prolong graft survival. All eight University Medical Centers in the Netherlands participated in this multicenter study. To improve the matching algorithm, we used as central hypothesis that the combined presence of class-I and -II single-antigen bead (SAB)-defined donor-specific HLA antibodies (DSA) prior to transplantation, non-HLA antibodies, the number of B- and/or T-cell epitopes recognized on donor HLA, and specific polymorphisms in effector mechanisms of IgG were associated with an increased risk for graft failure. The purpose of this article is to relate the results obtained from the PROCARE consortium study to other studies published in recent years. The clinical relevance of SAB-defined DSA, complement-fixing DSA, non-HLA antibodies, and the effector functions of (non)-HLA-antibodies will be discussed.