PIRCHE-II scores prove useful as a predictive biomarker among kidney transplant recipients with rejection: An analysis of indication and follow-up biopsies

Abstract

BackgroundIndication biopsies for deterioration of kidney allograft function often require follow-up biopsies to assess treatment response or lack of improvement. Immune-mediated injury, namely borderline rejection (BLR), T-cell mediated rejection (TCMR), or antibody-mediated rejection (ABMR), results from preformed or de novo alloreactivity due to donor and recipient HLA-mismatches. The impact of HLA-mismatches on alloreactivity is determined by highly immunogenic HLA-epitopes.MethodsWe analyzed 123 kidney transplant recipients (KTRs) from 2009 to 2019 who underwent a first indication and a follow-up biopsy. KTRs were divided into three groups according to the first biopsy: No rejection (NR)/BLR (n=68); TCMR (n=21); ABMR (n=34). The HLA-derived epitope-mismatches were calculated using the Predicted Indirectly Recognizable HLA-Epitopes (PIRCHE-II) algorithm.ResultsGroup NR/BLR: KTRs with higher total PIRCHE-II scores were more likely to develop TCMR in the follow-up biopsy (p=0.031). Interestingly, these differences were significant for both HLA-class I- (p=0.017) and HLA-class II-derived (p=0.017) PIRCHE-II scores. Group TCMR: KTRs with ongoing TCMR in the follow-up biopsy were more likely to show higher total PIRCHE-II scores (median 101.50 vs. 74.00). Group ABMR: KTRs with higher total PIRCHE-II scores were more likely to show an increase in the microvascular inflammation score in the follow-up biopsy. This difference was more pronounced for the HLA-class II-derived PIRCHE-II scores (median 70.00 vs. 31.76; p=0.086).ConclusionsPIRCHE-II scores may prove useful as a biomarker to predict the histopathological changes of immune-related injury from a first indication to a follow-up biopsy. This immunological risk stratification may contribute to individualized treatment strategies.

Association between PIRCHE‐II scores and de novo allosensitization after reduction of immunosuppression during SARS‐CoV‐2 infection in kidney transplant recipients

“…However, this has been linked to an increased risk of allosensitization and subsequent rejection. Recently, our own and other work have shown that the PIRCHE‐II scores are suitable biomarkers for better risk stratification in different immunological risk situations 20–22 . In the context of the current SARS‐CoV‐2 pandemic and other immunosuppression‐associated opportunistic infections, it seems particularly important to improve risk stratification for allosensitization in the case of reduced immunosuppression.…”

Histocompatibility Testing: A Fundamental Aspect of Renal Transplant Workup

“…This is important for organ and tissue transplants, because eplet mismatches can affect the success of the procedure. By evaluat-ing these mismatches, the tool helps to optimize donor selection, potentially improving transplant outcomes [30,[50][51][52].…”

An Integrated Approach Using HLAMatchmaker and Pirche II for Epitopic Matching in Pediatric Kidney Transplant—A Romanian Single-Center Study

“…One of these promising theoretical approaches is matching based on the Predicted Indirectly Recognizable HLA Epitopes (PIRCHE-II) algorithm and it has shown the potential to improve graft survival. The score is calculated via the PIRCHE-II algorithm using the theoretical number of the donor's HLA-epitopes, which contain 9 amino acids that can induce an indirect alloreactive response, specifically involving the CD4+ T-cell recognition of HLA class-II presented donor HLA-peptides [12]. Hence, the algorithm's aim is to identify HLA epitopes from the donor that can be displayed by the recipient's HLA-DRB1 alleles, but which are not present in their own HLA-A, -B, -C, -DRB1 and -DQB1alleles.…”