Computational Approaches to Facilitate Epitope-Based HLA Matching in Solid Organ Transplantation

Abstract

Epitope-based HLA matching has been emerged over the last few years as an improved method for HLA matching in solid organ transplantation. The epitope-based matching concept has been incorporated in both the PIRCHE-II and the HLAMatchmaker algorithm to find the most suitable donor for a recipient. For these algorithms, high-resolution HLA genotype data of both donor and recipient is required. Since high-resolution HLA genotype data is often not available, we developed a computational method which allows epitope-based HLA matching from serological split level HLA typing relying on HLA haplotype frequencies. To validate this method, we simulated a donor-recipient population for which PIRCHE-II and eplet values were calculated when using both high-resolution HLA genotype data and serological split level HLA typing. The majority of the serological split level HLA-determined ln(PIRCHE-II)/ln(eplet) values did not or only slightly deviate from the reference group of high-resolution HLA-determined ln(PIRCHE-II)/ln(eplet) values. This deviation was slightly increased when HLA-C or HLA-DQ was omitted from the input and was substantially decreased when using two-field resolution HLA genotype data of the recipient and serological split level HLA typing of the donor. Thus, our data suggest that our computational approach is a powerful tool to estimate PIRCHE-II/eplet values when high-resolution HLA genotype data is not available.

Inaccuracies in epitope repertoire estimations when using multilocus allele‐level HLA genotype imputation tools

“…Epitopes likely to be bound (IC50 < 1000) in one of the recipient's HLA‐DRB1 molecules binding grooves are considered as PIRCHE‐II. The PIRCHE‐II algorithm (https://www.pirche.org/) determines the number of HLA‐derived mismatches in T‐cell epitopes for each donor‐recipient pair . The Immune Epitope Database (IEDB, http://www.iedb.org/) is a free resource, which allows searches of T‐ and B‐cell epitopes, including those involved in transplantation, that have been studied in humans and other animal species.…”

How the definition of acceptable antigens and epitope analysis can facilitate transplantation of highly sensitized patients with excellent long-term graft survival

“…Only in case both B cells and T cells recognize epitopes derived from the allogeneic HLA molecules, IgG antibodies will be produced. A first algorithm has been developed to predict the presence and number of such immunogenic peptides [35]. Two recent studies showed a correlation between low match grades for indirectly recognizable T cell epitopes and the formation of de novo donor-specific antibodies [36], as well as inferior long-term graft survival [37].…”

The quest to decipher HLA immunogenicity: Telling friend from foe

“…Advances in HLA typing and HLA antibody testing over the past two decades transformed our ability to assess donor/recipient compatibility in the context of organ transplantation. Beginning from serologic donor/recipient HLA matching through emphasis on avoidance of preformed donor‐specific HLA antibodies (DSAs), current approaches delve into amino acid sequences of HLA alleles, assessing the so‐called molecular mismatch between donor and recipient, using one or more of the currently available tools: HLAMatchmaker, Amino‐Acid comparison, Electrostatic Mismatch Score (EMS), or PIRCHE—Predicted Indirectly ReCognizable HLA Epitopes presented by recipient HLA‐Class II antigens . A short description of each method is provided in the supplemental material.…”