title: 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-determinedln(PIRCHE-II)/ln(eplet)values did not or only slightly deviate from the reference group of high-resolution HLA-determinedln(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.
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Kirsten
authors.identifier: 0000-0002-1689-8383
authors.initials: K
authors.lastname: Geneugelijk
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Wissing
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: Koppenaal
authors.affiliation: PIRCHE AG, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Niemann
authors.affiliation: Laboratory of Translational Immunology, University Medical Center Utrecht, Utrecht, Netherlands.
authors.forename: Eric
authors.identifier: 0000-0001-9441-1019
authors.initials: E
authors.lastname: Spierings
mesh_terms: D000465:Algorithms; D019295:Computational Biology; D018985:Epitopes, B-Lymphocyte / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006650:Histocompatibility Testing / Q000379:methods*; D006801:Humans; D007518:Isoantibodies / Q000378:metabolism; D016377:Organ Transplantation; D015203:Reproducibility of Results; D012984:Software; D014019:Tissue Donors; D066027:Transplant Recipients; D044465:White People
chemical_list: D018985:Epitopes, B-Lymphocyte; D006680:HLA Antigens; D007518:Isoantibodies