Mapping molecular HLA typing data to UNOS antigen equivalents for improved virtual crossmatch

BACKGROUND Histocompatibility labs must convert molecular HLA typing data to antigen equivalencies for entry into the United Network for Organ Sharing (UNOS) UNet system. While an Organ Procurement and Transplantation Network (OPTN) policy document provides general guidelines for conversion, the process is complex because no antigen mapping table is available. We present a UNOS antigen equivalency table for all IPD-IMGT/HLA alleles at the A, B, C, DRB1, DRB3/4/5, DQA1, and DQB1 loci. METHODS An automated script was developed to generate a UNOS antigen equivalency table. Data sources used in the conversion algorithm included the World Marrow Donor Association (WMDA) antigen table, the HLA Dictionary, and UNOS-provided tables. To validate antigen mappings, we converted National Marrow Donor Program (NMDP) high resolution allele frequencies to antigen equivalents and compared with the UNOS Calculated Panel Reactive Antibodies (CPRA) reference panel. RESULTS Normalized frequency similarity scores between independent NMDP and UNOS panels for 4 US population categories (Caucasian, Hispanic, African American and Asian/Pacific Islander) ranged from 0.85 to 0.97, indicating correct antigen mapping. An open source web application (ALLele to ANtigen ("ALLAN")) and web services were also developed to map unambiguous and ambiguous HLA typing data to UNOS antigen equivalents based on NMDP population-specific allele frequencies (http://www.transplanttoolbox.org). CONCLUSIONS Computer-assisted interpretation of molecular HLA data may aid in reducing typing discrepancies in UNet. This work also sets a foundation for molecular typing data to be utilized directly in the UNet match run as well as the virtual crossmatch process at transplant centers.