Expansion of molecular mismatch scores to guide clinical management of kidney transplant patients.

PURPOSE OF REVIEW: Optimizing outcomes for kidney transplant recipients requires both minimizing premature death related to over-immunosuppression and avoiding alloimmune injury associated with under-immunosuppression. Both of these goals require a precise understanding of the alloimmune risk faced by the recipient. Although the assessment of HLA mismatch at the antigen level lacks refinement, molecular mismatch has been shown to increase precision in alloimmune risk assessment. This review discusses the expansion of the role of molecular mismatch in optimizing the clinical management of kidney transplant recipients.

RECENT FINDINGS: Eplet mismatch has been reported as a reliable predictive biomarker for immunosuppression adequacy and to identify recipients who are less likely to tolerate minimization or nonadherence. Human leukocyte antigen DR and/or DQ (HLA-DR/DQ) single-molecule mismatch has also been validated as a prognostic biomarker in immunosuppression conversion studies, providing a precise, individualized assessment of alloimmune risk to guide decision-making regarding immunosuppression. PIRCHE-II scores have been observed to potentiate the risk of dnDSA development. The use of molecular mismatch can also be expanded to personalized posttransplant alloimmune monitoring and dnDSA surveillance.

SUMMARY: To facilitate precision medicine in transplantation, molecular mismatch has the potential to serve as a prognostic and predictive biomarker for primary alloimmunity.