HLA Genotype Imputation Results in Largely Accurate Epitope Mismatch Risk Categorization Across Racial Groups

Area of Science:

• Transplantation immunology
• Genetics
• Bioinformatics

Background:

• Biomarkers predicting posttransplant alloimmunity are crucial for long-term graft survival.
• Molecular mismatch analysis, evaluating HLA epitope mismatches, classifies rejection risk.
• Imputation of high-resolution HLA genotyping is necessary when data is unavailable, but its accuracy impact on risk assessment is unclear.

Purpose of the Study:

• To assess the impact of imputation on molecular mismatch analysis.
• To determine if imputation inaccuracies affect clinical risk assessment for graft rejection.
• To validate imputation's reliability across different racial groups in kidney transplantation.

Main Methods:

• Constructed surrogate donor-recipient pairs with high- and low-resolution HLA genotyping.
• Assessed imputation impact on molecular mismatch analysis in racially concordant and discordant cohorts.
• Evaluated imputation effect in a real-world, racially diverse validation cohort of renal transplant pairs.

Main Results:

• Imputation preserved molecular mismatch risk category in 90.5%-99.6% of racially concordant pairs and 92.5%-100% of discordant pairs in surrogate cohorts.
• In a validation cohort (72% racially discordant), imputation preserved risk category in 97.1% of pairs.
• Imputation demonstrated high reliability across diverse racial groups.

Conclusions:

• Imputation reliably preserves molecular mismatch risk assessment.
• The findings support the use of imputation in molecular mismatch analysis for clinical decision-making.
• This approach can aid in improving long-term graft survival through accurate risk stratification.