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THE FUTURE IS EPITOPES

This study outlines a Europe-wide strategy aimed at improving the transplantation process for highly sensitized patients by utilizing Acceptable HLA Mismatches. It analyzes 208 HLA populations from 399,305 individuals, providing insights on population-specific epitope frequencies derived from raw genotyping data. The HLA Epitope Registry is a vital resource, cataloging 526 epitopes with confirmed, provisional, and predicted antibody reactivity data. This research facilitates the efficient matching of donors and recipients based on individual epitope frequencies, ultimately enhancing transplant success rates.

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THE FUTURE IS EPITOPES

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  1. THE FUTURE IS EPITOPES DEREK MIDDLETON DAVID LOWE ROYAL LIVERPOOL UNIVERSITY HOSPITAL R

  2. FP7 EC EUROSTAM • A EUROpe-wide Strategy to enhance • Transplantation of highly sensitized patients • on basis of Acceptable HLA Mismatches

  3. European populations on www.allelefrequencies.net Europe: 208 HLA pops from 399,305 individuals

  4. Example of population frequencies in AFND Azores central Islands n=59

  5. Examples of Class I Epitopes • Epitopes are sorted according to their sequence positions in each locus • Distinct sequence position numbers and polymorphic residue descriptions with standard single letter amino acid codes, e.g. 62GE

  6. HLA Epitope Registry Website http://epregistry.ufpi.br • Total of 526 epitopes • Confirmed = 57 • Antibody Reactivity Data • Provisional = 103 • Partial Antibody Reactivity Data • Predicted = 366 • No Antibody Reactivity Data

  7. HLA Epitope Frequencies Molecular locations of epitopes in HLA-A24 molecule (Duquesnoy, 2011) • Epitope Frequencies in populations: • Estimate epitope frequencies for all populations stored in AFND • Link data with HLA Epitope Registry website

  8. Sum of Epitopes From Allele Frequencies vs. Frequency of Individuals Having the Epitope Two Loci One locus • Frequency of Individuals Expressing Epitope was calculated from HLA raw data • Using raw data is the most accurate way to determine Epitope Frequency in Populations Sum of Epitope Allele Count Count of Individuals Expressing Epitope

  9. HLA−A and −B Epitope Frequencies in World Populations Epitope Frequencies were obtained from raw genotyping data

  10. High Resolution Alleles from HLA-A*01 Antigenic Group by Epitopes in Position 9

  11. Estimation of epitope frequencies from haplotype data England North West Frequencies of epitopes obtained from raw genotyping data Frequencies of epitopes estimated from haplotype data

  12. Single Donor Mismatch; Donor A32, recipient A1 Donor mm: A32 9 Identified epitopes, none present on HLA-A1 167W 253Q 167W 253Q 109L+ 131R 80I 80I 138M+ 144Q 253Q 80I+ 109L 109L 109L Cw7 Cw6 A29 B57 A1 B8 A32 80I+ 82L+ 82L+ 109L+ 131R 109L+ 163T 109L+ 163T 138M+ 144Q 167W 167W 167W Recipient HLA

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