Abstract 4361217: The Impact of Donor-Recipient Race Matching on Development of De Novo Donor-Specific Antibodies After Heart Transplantation

Background: Heart transplantation remains the definitive treatment for end-stage heart failure, but outcomes vary by race. Black patients demonstrate worse survival and race matching does not improve mortality. Various mechanisms have been posited to explain this discrepancy, including immunologic factors. Development of de novo donor-specific antibodies (dnDSA) is known to increase mortality. We sought to study the effect of donor-recipient race matching in heart transplantation on the development of dnDSA and mortality. Methods: We conducted a retrospective cohort study of 426 adult heart transplant recipients admitted to a large tertiary healthcare system from 2011-2024. Races were categorized as White, Black, Asian, American Indian, and Hawaiian. Recipients were categorized as race-matched (n=315) or unmatched (n=111). The time to dnDSA detection was analyzed using the Fine-Gray method, with death treated as a competing risk. Mortality was estimated using Kaplan-Meier survival analysis. Multivariable Cox regression models using both donor and recipient variables were used to assess the impact of risk factors on dnDSA development and mortality. We calculated total HLA match based on HLA-A, B, and DR (score 0-6). Variable selection used stepwise regression (p<0.2 for inclusion), with race match forced into all models. Results: Race-matched recipients had a significantly higher cumulative incidence of dnDSA at year 1 and over the entire follow-up period (Figure 1). In our adjusted model, race matching (HR 3.64, 95% CI 1.88–7.06) remained a significant predictor of dnDSA development as did Black recipient race (HR 3.27, 95% CI 1.70–6.28), greater HLA mismatch score, recipient insurance and BMI (Table 1). In contrast, neither race matching (Figure 2) nor dnDSA were associated with all-cause mortality. Conclusion: Our study demonstrates that donor-recipient race matching is independently associated with an increased risk of dnDSA development following heart transplantation even after controlling for recipient race and HLA matching. The mechanisms underlying this surprising finding remain unclear and underscore the genetic heterogeneity that exists within race. However, race matching and dnDSA were not associated with differences in mortality. Our findings highlight the complex immunologic interplay between race concordance and dnDSA development, warranting further investigation into individualized risk stratification beyond traditional HLA matching.