# Simulation of prospective PIRCHE-II molecular matching in Canada: a feasibility study

## TL;DR

This study evaluates the feasibility of using the PIRCHE-II model for molecular matching in kidney transplants in Canada, finding it more practical for specific HLA loci.

## Contribution

The study introduces a test-bed analysis of PIRCHE-II epitope-optimized allocation in a Canadian transplant population.

## Key findings

- Molecular matching across all 5 HLA loci is achievable in less than 10% of patients.
- Matching with a low PIRCHE-II score at DRB1 or DQB1 loci is possible in over 90% of patients.
- Allocation probabilities are influenced by factors like waiting-list size and ABO compatibility.

## Abstract

Organ allocation to minimize Human Leukocyte Antigens (HLA) disparity between donor and recipient has been shown to improve outcomes but is limited by the enormous HLA diversity. PIRCHE-II in silico model considers the HLA peptide binding characteristics of recipients to quantitate molecular compatibility. Having previously published the feasibility of including B-cell eplets into simplified, simulated match algorithms, here we assess the feasibility of using PIRCHE-II epitope optimised allocation, in a cohort of ~1500 heterogenous renal patients and donors within the National Canadian organ transplant program.

This test-bed-only analysis provides critical first steps to understanding if prospective matching is indeed feasible, in a Canadian transplant population.

Simplified base-case simulation models optimizing for PIRCHE-II score demonstrate that molecular matching across all 5 HLA gene loci (A, B, C, DR, DQ) is achievable in <10% of patients, and hence would not be realistic for clinical allocation. In contrast, molecular matching with a low PIRCHE-II score at the principal HLA class II DRB1 or DQB1 loci may be achieved in over 90% of patients compared with the base-case scenario.

In reality, the precise matching probability is governed by multiple factors including waiting-list size, donor organ factors, and other allocation restrictions (i.e. ABO blood type, presence of anti-HLA antibodies, clinical urgency), which would further impact match probability.