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Review
. 2019 Aug;94(2):129-140.
doi: 10.1111/tan.13581. Epub 2019 Jun 18.

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

Elena G Kamburova  1 , Andries Hoitsma  2 , Frans H Claas  3 , Henny G Otten  1 ; PROCARE Consortium
Affiliations
Review

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

Elena G Kamburova et al. HLA. 2019 Aug.

Abstract

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.

Keywords: HLA antibodies; HLA epitope; kidney transplantation; non-HLA antibodies.

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Conflict of interest statement

The authors have declared no conflicting interests.

Figures

Figure 1
Figure 1
Overview of the PROfiling Consortium on Antibody Repertoire and Effector (PROCARE) ICT infrastructure with the different clinical and laboratory data. NOTR, Dutch Organ Transplant Registry; PIRCHE, Predicted Indirectly ReCognizable HLA Epitopes
Figure 2
Figure 2
Flow chart for the inclusion and exclusion of transplantations for the different analyses. DSA, donor‐specific HLA antibodies; SNP, single nucleotide polymorphisms
Figure 3
Figure 3
A, Assignment of donor‐specific antibodies (DSA) using the single‐antigen bead (SAB) assay and serological split‐level donor HLA‐A, ‐B, ‐DRB1, −DQ typing. If a bead is positive (ie, A*24:02) and this antigen was also present on the donor HLA (ie, A24), we assigned this as a DSA. (B) Death‐censored 10‐year graft survival stratified according to the number of pre‐transplant DSA for 1487 living‐donor transplantations and 3237 deceased‐donor transplantations
Figure 4
Figure 4
Assignment of donor‐epitope specific antibodies (DESA) using the single‐antigen bead (SAB) assay and the most likely high‐resolution HLA‐A, ‐B, ‐C, ‐DRB1, ‐DRB3‐5, −DQA1, ‐DQB1 typing for donor and recipient. First, the HLA typing's were converted into epitopes. Next, the recipient and donor epitopes were compared, and epitopes of the donor HLA that were not present on the recipient HLA were assigned as mismatched. Also, the results of the SAB assay were converted into epitopes. If an epitope, that was only present on positive beads, was one of the mismatched epitopes, we assigned this as a DESA
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