PIRCHE-II Is Related to Graft Failure after Kidney Transplantation

Abstract

Individual HLA mismatches may differentially impact graft survival after kidney transplantation. Therefore, there is a need for a reliable tool to define permissible HLA mismatches in kidney transplantation. We previously demonstrated that donor-derived Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA class II (PIRCHE-II) play a role in de novo donor-specific HLA antibodies formation after kidney transplantation. In the present Dutch multi-center study, we evaluated the possible association between PIRCHE-II and kidney graft failure in 2,918 donor–recipient couples that were transplanted between 1995 and 2005. For these donors–recipients couples, PIRCHE-II numbers were related to graft survival in univariate and multivariable analyses. Adjusted for confounders, the natural logarithm of PIRCHE-II was associated with a higher risk for graft failure [hazard ratio (HR): 1.13, 95% CI: 1.04–1.23, p = 0.003]. When analyzing a subgroup of patients who had their first transplantation, the HR of graft failure for ln(PIRCHE-II) was higher compared with the overall cohort (HR: 1.22, 95% CI: 1.10–1.34, p < 0.001). PIRCHE-II demonstrated both early and late effects on graft failure in this subgroup. These data suggest that the PIRCHE-II may impact graft survival after kidney transplantation. Inclusion of PIRCHE-II in donor-selection criteria may eventually lead to an improved kidney graft survival.

Caveats of HLA antibody detection by solid‐phase assays

“…In case of a de novo immune response, the load of mismatched epitopes—and even more their individual immunogenicity—might be the driving force for rejection. Novel “memory” assays and sophisticated software algorithms (i.e., HLA Matchmaker, PIRCHE II) have been developed to address these gaps . All these tools and their further improvement rely heavily on SAB analyses.…”

Novel insights into non‐HLA alloimmunity in kidney transplantation

“…Currently, however, it is impossible to estimate which of the presentable peptides will eventually induce a T cell response. Nevertheless, evaluation of the PIRCHE‐II score in two large kidney transplant cohorts confirmed its association with dnDSA occurrence and long‐term kidney allograft survival independent of eplet mismatch .…”

Matching donor and recipient based on predicted indirectly recognizable human leucocyte antigen epitopes

“…Recently, we investigated the possible association between PIRCHE‐II and kidney graft failure in a large cohort consisting of all kidney transplantations that were performed in the Netherlands between 1995 and 2005 (Geneugelijk et al, ). When adjusted for confounders, increasing PIRCHE‐II numbers appeared to be a risk factor for kidney graft failure after transplantation, in particular in patients who had their first transplant (Geneugelijk et al., ). These results support the large independent parallel study reported by Lachmann et al.…”

“…As the de novo formation of DSA may lead to allograft rejection after transplantation (Everly et al, 2013;Zhang et al, 2005), a relation between PIRCHE-II numbers and allograft rejection after transplantation is expected. Recently, we investigated the possible association between PIRCHE-II and kidney graft failure in a large F I G U R E 3 Two illustrative examples of predicted indirectly recognizable human leucocyte antigen (HLA) epitopes-(PIRCHE) II derived from different HLA molecules for different donor-recipient combinations cohort consisting of all kidney transplantations that were performed in the Netherlands between 1995 and 2005 (Geneugelijk et al, 2018). When adjusted for confounders, increasing PIRCHE-II numbers appeared to be a risk factor for kidney graft failure after transplantation, in particular in patients who had their first transplant (Geneugelijk et al, 2018).…”