P078HLA-DRB3/4/5 allele and haplotype frequencies in Koreans and its application to counting DR eplet mismatch

Abstract

Aim Allele level interpretation of HLA DR-3/4/5 is encouraged as low-expression loci mismatch can affect the outcome of organ transplantation. Here we assess the HLA-DRB3/4/5 allele frequency in Korean population and report the occurrence rate of post-transplantation HLA-DR donor specific antigen (DSA) according to eplet mismatches including HLA-DRB1 and HLA-DRB3/4/5. Methods High resolution genotyping of HLA-DRB3/4/5 at 6-digit level was done using blood samples from 150 unrelated healthy Koreans. Regarding assessment of the effect on organ transplantation, there were 272 patients with pre- and post-op panel reactive antibody (PRA) results during September 1st, 2012 and August 31th, 2017. Their post-transplantation de novo DSA occurence was analyzed by HLA-DR eplet mismatches of HLA-DRB1 and HLA-DR3/4/5. Results Four HLA-DRB3 alleles, three HLA-DRB4 alleles and three HLA-DRB5 alleles were found at 6-digit level (Table). Total 32 HLA-DRB1-DRB3/4/5 haplotype combinations were found (data not shown). The number of eplet mismatch with no post-transplantation de novo DSA was seven for HLA-DR and cumulative DSA frequency was observed up to 9.8% (Image). Conclusions HLA-DRB3/4/5 allele frequency and HLA-DRB1-DRB3/4/5 haplotype frequency were analyzed at 6-digit level for the first time in Koreans. Our result demonstrates that degree of HLA-DR eplet mismatches of all HLA-DR loci could affect generation of post-op de novo DSA. These results will be useful for PRA interpretation and understanding the impact of low-expression loci on organ transplantation.