De Novo Donor-Specific Anti-HLA Antibody Risk Stratification in Kidney Transplantation Using a Combination of B Cell and T Cell Molecular Mismatch Assessment

Elaine Chou-Wu ^1* Matthias Niemann ² Danny Youngs ¹ Idoia Gimferrer ¹

• ¹ Bloodworks Northwest, Seattle, California, United States
• ² PIRCHE AG, Berlin, Berlin, Germany

Introduction: The presence of de novo donor-specific antibody (dnDSA) has detrimental effect on allograft outcomes in kidney transplantation. As humoral responses in transplantation are elicited targeting non-self epitopes on donor HLA proteins, assessing HLA mismatches at the molecular level provides a refined means for immunological risk stratification. Methods: In the present study, we utilized three HLA molecular mismatch assessment algorithms, Snow, HLAMatchmaker, and PIRCHE-II, to evaluate the independent and synergistic association of B cell and T cell epitope mismatches with dnDSA development in a cohort of 843 kidney transplant recipients. Results: Our results demonstrated that B cell and T cell epitope mismatches at HLA Class I and DRB1/DQB1 loci are remarkably increased in dnDSA-positive recipients, even after normalization by allele mismatch numbers in individual study subjects. Furthermore, elevated Snow, verified eplet mismatches, and PIRCHE-II scores are significantly associated with dnDSA occurrence individually and in combination. Conclusion: Our findings highlight the value of utilizing B cell and T cell epitope mismatch evaluation in living donor selection and immunological risk stratification to improve transplant outcomes.