Clinical Applicability of 2-Field High-Resolution and Extended HLA-Allele Typing in Deceased Donor Kidney Allocation

Abstract

HLA-compatibility remains an important triage test for deceased donor kidney allocation. Low–intermediate resolution donor HLA-typing is typically available at allocation, but its accuracy in assigning pre-transplant donor-specific anti-HLA antibody (DSA) and HLA mismatches compared to 2-field high-resolution typing is poorly characterised. Consecutive deceased donor/recipient pairs from a single centre between 2016 and 2020 were included. Majority of donor typing at HLA-ABDRB1 loci were performed at low–intermediate resolution, with 2-field high-resolution NGS typing across extended loci performed by NGS-technique post-transplantation. We compared the two typing methods for (1) accuracy of pre-transplant DSA assignment; (2) misassignment of HLA-antigen/allele mismatches and performance of each model for acute rejection and (3) proportion of recipients who developed de novo DSA (dnDSA) when matched at antigen but mismatched at allele level. Of 179 deceased donor/recipient pairs, 157 donors had low–intermediate resolution typing and 22 with high-resolution ONT typing. Sixty-two recipients (35%) had potential pre-transplant DSAs, with incorrect assignment of allele-specific Class I and II actual DSAs in 31% and 53% of cases, respectively. NGS typing identified 59 (33%) additional HLA-DRB1 allele mismatches. ONT typing accurately assigned pre-transplant DSAs and allele mismatches in all cases. Seven (4%) recipients with antigen/allele level discordance developed dnDSAs, majority HLA-DQ antibodies. Two-field high-resolution donor HLA typing may provide a more accurate transplant immunological risk assessment and identify those at risk of developing dnDSA to matched HLA antigen.