Maintaining updated DNA-based HLA assignments in the National Marrow Donor Program Bone Marrow Registry

Area of Science:

• Immunogenetics
• Bioinformatics

Background:

• The National Marrow Donor Program (NMDP) manages a large registry of volunteer stem cell donors.
• Accurate Human Leukocyte Antigen (HLA) typing is critical for successful hematopoietic stem cell transplantation.
• The discovery of new HLA alleles impacts the accuracy of DNA-based typing assignments.

Purpose of the Study:

• To implement and evaluate a standardized approach for DNA-based HLA-DRB typing assignments within the NMDP.
• To assess the impact of new allele discoveries on HLA typing results.
• To develop and validate software for interpreting HLA typing data.

Main Methods:

• Applied a standardized set of sequence-specific oligonucleotide (SSO) reagents for DRB typing on 371,187 donor samples.
• Electronically transmitted hybridization results to the NMDP for processing.
• Utilized a dedicated software program to interpret primary data into HLA assignments, rejecting those below a specified resolution level.
• Compared NMDP software assignments with those from 14 participating laboratories' local software programs.

Main Results:

• NMDP software achieved 90.5% concordance with laboratory assignments.
• Discrepancies were attributed to variations in typing resolution, inclusion of secondary DRB loci, summarization of alternative assignments, and data submission errors.
• Re-interpreting 1999 data with alleles defined in July 2000 revealed that 74% of HLA-DRB assignments were altered by new allele descriptions.

Conclusions:

• The developed NMDP software effectively standardizes HLA-DRB typing and improves assignment accuracy.
• The continuous discovery of new HLA alleles necessitates adaptive software solutions for accurate donor registry management.
• This standardized approach is crucial for maintaining the integrity and utility of large donor registries for transplantation.