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Abstract: TH-OR28

HLA-DR/DQ Single Molecule Eplet Mismatch and Formation of De Novo Donor-Specific Anti-HLA Antibodies After Kidney Transplantation in Children

Session Information

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Sigurjonsdottir, Vaka Kristin, University of Miami School of Medicine, Miami, Florida, United States
  • Piburn, Kim H., Stanford University School of Medicine, Stanford, California, United States
  • Grimm, Paul C., Stanford University School of Medicine, Stanford, California, United States
Background

Eplet mismatches in HLA at the single-molecule level, have been identified as a prognostic biomarker for primary alloimmunity. Limited evidence exists on the optimal risk stratification cut-offs in racially diverse pediatric patients receiving kidney transplantation

Methods

Children transplanted from 1/1/2010-3/1/2018 at Stanford, with >12-month follow-up, were included. High-resolution HLA typing was performed using next-generation sequencing. Outcome: time to de novo donor specific antibody (dnDSA) formation. dnDSA were screened at the time of transplant, 1, 2, 3, 6, and 12 months following, at least annually thereafter, and as clinically indicated. ROC analysis at the DR and DQ loci was performed to determine risk categories based on total and single-molecule eplet mismatch thresholds. Survival analysis was performed by the Kaplan-Meier method using the log-rank test for significance

Results

A total of 233 patients were identified. Our preliminary results include high-resolution typing for 174. Of those, median age was 13 (IQR 9), 23.6% had living donor transplant and 48.3% were female. The Median follow-up time was 36.5 months (IQR 36). 46.0% formed Anti-HLA class II dnDSA. Patients with an eplet mismatch sum of HLA DR > 6 and/or DQ > 4 (n=161) had increased risk of HLA-DR/DQ dnDSA formation, p=0.006. Similarly, patients with single-molecule HLA-DR > 5 and/or DQ > 4 had an increased risk of HLA-DR/DQ dnDSA development. [Figure]

Conclusion

Single-molecule eplet mismatch and total eplet mismatch are associated with an increased risk of dnDSA formation. Assessing a patient’s individual risk based on donor/recipient HLA-DR/DQ eplet mismatches may guide immunosuppression regimen in the post-transplant period and predict adverse outcomes.

Funding

  • Private Foundation Support