Mismatch epitope load predicts de novo‐DSA‐free survival in pediatric liver transplantation.

Background: Our knowledge of de novo anti‐HLA donor‐specific antibodies (dnDSA) in liver transplantation continues to be defined. We hypothesized that differences of HLA‐DR/DQ mismatches can improve precision in alloimmune risk categorization and be applied to tailor immunosuppression. Methods: A retrospective chart review of 244 pediatric patients consecutively transplanted at our center between 2003 and 2019 was performed to identify patients tested for dnDSA. Records were queried for: demographics, pre‐transplant diagnosis, biopsy‐proven T‐cell‐mediated rejection (TCMR), radiology proven biliary complications, tacrolimus trough levels, dnDSA characteristics, and HLA typing. The eplet mismatch analyses were performed using HLAMatchmaker™ 3.1. All statistical analyses were conducted using R software version 3.40. Results: There were 99 dnDSA‐negative patients and 73 dnDSA‐positive patients (n = 70 against class II and n = 3 against class I and II). ROC analysis identified optimal cutoff of eplet mismatch load for dnDSA and defined risk groups for an alloimmune outcome. Kaplan–Meier curves and log‐rank tests showed high eplet mismatch load was associated with shorter dnDSA‐free survival (log‐rank p =.001). Multivariable Cox regression models showed that tacrolimus coefficient of variation and tacrolimus mean levels were significantly associated with dnDSA‐free survival (p <.001 and p =.036). Fisher's exact test showed that dnDSA was associated with an increased likelihood of TCMR (OR 14.94; 95% CI 3.65 – 61.19; p <.001). Patients without TCMR were more likely to have dnDSA to HLA‐DQ7 and less likely to have dnDSA to HLA‐DQ2 (p =.03, p =.080). Conclusions: Mismatched epitope load predicts dnDSA‐free survival in pediatric liver transplant, while dnDSA specificity may determine alloimmune outcome. [ABSTRACT FROM AUTHOR]