REVIEW
Transpl. Int.
The progress and challenges of implementing HLA molecular matching in clinical practice
Department of Internal Medicine, Division of Nephrology & Transplantation, Erasmus MC Transplant Institute, Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
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Abstract
HLA molecular matching in solid organ transplantation in the form of eplets, solvent-accessible amino acids or PIRCHE-II has been proposed as a more granular method than HLA matching on the antigen level.While many studies have shown the association between molecular mismatches and de novo donorspecific antibody formation, rejection and graft loss, evidence for prospective molecular matching in allocation is currently lacking, and the actual practical implementation and feasibility of molecular matching remains unclear. In this review the various potential applications of molecular matching in transplantation are discussed, including 1) organ allocation in deceased donor programs, 2) living donor selection, 3) increasing the transplantability of highly sensitized patients and 4) risk stratification to facilitate personalized immunosuppressive management, along with the challenges and gaps in current knowledge regarding these approaches. While clinical application of molecular mismatch analysis in solid organ transplantation holds promise, the fundamentals of HLA-specific antibody biology and epitopeparatope interactions should be further elucidated. This will aid in unraveling the factors that affect the relative immunogenicity of HLA molecular mismatches in order to start using molecular matching in clinical transplantation.
Summary
Keywords
HLA, Eplet, kidney transplantation, molecular mismatch, organ allocation
Received
01 April 2025
Accepted
03 July 2025
Copyright
© 2025 Bezstarosti and Heidt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Suzanne Bezstarosti, suzanne.bezstarosti@gmail.com; Sebastiaan Heidt, s.heidt@erasmusmc.nl
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