Human leukocyte antigen molecular mismatch to risk stratify kidney transplant recipients.

Abstract

Stalled drug development and the lack of improvement in long-term graft survival reflect the unmet need for prognostic and predictive biomarkers in transplantation. Although conventional human leukocyte antigen (HLA) mismatch is too imprecise to fulfill this need, HLA molecular mismatch increases the precision in alloimmune risk assessment by quantifying the difference between donors and recipients at the molecular level. Within each conventional HLA mismatch, recipients exhibit a wide range of HLA molecular mismatches with their donors. Quantifying HLA molecular mismatch improves the precision of alloimmune risk assessment for de novo donor-specific antibody development (dnDSA). Alloimmune risk categories developed analyzing dnDSA development were also found to correlate with T-cell-mediated rejection, antibody-mediated rejection, and all cause graft loss in adjusted and unadjusted models. All alloimmunity is driven by differences between donors and recipients at the molecular level. HLA molecular mismatch may represent a fast, reproducible, cost-effective, way to improve alloimmune risk assessment at the time of transplantation to move the field towards precision medicine.