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Abstract: TH-PO1058

Association of Eplet Mismatch Load and Allograft Injury in Kidney Transplant Recipients

Session Information

Category: Transplantation

  • 2002 Transplantation: Clinical

Authors

  • Molnar, Miklos Zsolt, University of Rochester Medical Center, Rochester, New York, United States
  • Toth, Fruzsina, University of Utah Health, Salt Lake City, United States
  • Holdaway, Kendon J., University of Utah Health, Salt Lake City, Utah, United States
  • Raghavan, Divya, University of Utah Health, Salt Lake City, Utah, United States
  • Marineci, Silviana, University of Utah Health, Salt Lake City, Utah, United States
  • Oygen, Suayp, University of Utah Health, Salt Lake City, Utah, United States
  • Fornadi, Katalin, University of Utah Health, Salt Lake City, Utah, United States
Background

Eplet mismatch load is a molecular measure of donor–recipient histocompatibility that has been associated with alloimmune outcomes after kidney transplantation. However, its relationship with comprehensive markers of early allograft injury remains incompletely defined.

Methods

In this single-center retrospective cohort study, we evaluated 683 adult kidney transplant recipients transplanted between January 2021 and December 2024. Eplet mismatch load was calculated at the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQA1, and HLA-DQB1 loci using the HLA Eplet Registry. The primary outcome was a composite of early allograft injury, defined as the occurrence of donor-specific antibodies, histologic rejection, molecular rejection assessed by the Molecular Microscope Diagnostic System, or elevation of donor-derived cell-free DNA within the first year after transplantation.

Results

During the first post-transplant year, 250 patients (37%) experienced the primary outcome. Median eplet mismatch load was significantly higher among patients with the primary outcome across all HLA loci, with the strongest differences observed at class II loci (HLA-DRB1: 15 vs 12; HLA-DQB1: 9 vs 7; both p<0.001). In adjusted Cox regression models, higher class II eplet mismatch load was independently associated with increased risk of the primary outcome (HLA-DRB1: hazard ratio 1.029 per one-eplet increase; 95% confidence interval 1.016–1.042; HLA-DQB1 (Figure): hazard ratio 1.043 per one-eplet increase; 95% confidence interval 1.025–1.061). Compared with zero eplet mismatch, high-risk class II eplet mismatch categories were associated with approximately twofold higher risk of early allograft injury. Associations for class I loci were weaker and less consistent after adjustment.

Conclusion

In conclusion, higher class II HLA eplet mismatch load was independently associated with early kidney allograft injury during the first post-transplant year. These findings support the use of eplet-based molecular matching as a baseline immunologic risk stratification tool in kidney transplantation.

Acknowledgment

This study was approved by the University of Utah Institutional Review Board (#IRB_00162331).

Funding

  • Private Foundation Support