Clinical kidney journal · 2026
Association of eplet mismatch load and allograft injury in kidney transplant recipients.
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Toth Fruzsina, Holdaway Kendon J, Raghavan Divya, Marineci Silviana, Oygen Suayp, Fornadi Katalin, Molnar Miklos Z
Аннотация
INTRODUCTION: 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 657 adult kidney transplant recipients who underwent transplantation 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 independent occurrence of de novo 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, 248 patients (37.7%) experienced the primary outcome. Median eplet mismatch load was significantly higher among patients with the primary outcome across most HLA loci. In adjusted Cox regression models, higher eplet mismatch load (per one-eplet increase) was independently associated with increased risk of the primary outcome for HLA-DRB1 (hazard ratio 1.025; 95% confidence interval 1.011-1.038), HLA-DQA1 (hazard ratio 1.075; 95% confidence interval 1.025-1.127), and HLA-DQB1 (hazard ratio 1.038; 95% confidence interval 1.020-1.057). Compared with zero eplet mismatch, high-risk class II eplet mismatch categories were associated with approximately two- to three-fold higher risk of early allograft injury. Associations for class I loci were weaker and pattern-dependent after adjustment.
CONCLUSION: In conclusion, a higher class II HLA-eplet mismatch load was independently associated with early kidney allograft injury during the first post-transplant year.
METHODS: In this single-center retrospective cohort study, we evaluated 657 adult kidney transplant recipients who underwent transplantation 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 independent occurrence of de novo 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, 248 patients (37.7%) experienced the primary outcome. Median eplet mismatch load was significantly higher among patients with the primary outcome across most HLA loci. In adjusted Cox regression models, higher eplet mismatch load (per one-eplet increase) was independently associated with increased risk of the primary outcome for HLA-DRB1 (hazard ratio 1.025; 95% confidence interval 1.011-1.038), HLA-DQA1 (hazard ratio 1.075; 95% confidence interval 1.025-1.127), and HLA-DQB1 (hazard ratio 1.038; 95% confidence interval 1.020-1.057). Compared with zero eplet mismatch, high-risk class II eplet mismatch categories were associated with approximately two- to three-fold higher risk of early allograft injury. Associations for class I loci were weaker and pattern-dependent after adjustment.
CONCLUSION: In conclusion, a higher class II HLA-eplet mismatch load was independently associated with early kidney allograft injury during the first post-transplant year.