HLA molecular mismatch – A step towards precision medicine in transplantation for individualized immune risk assessment and immunosuppression
- 1Department of Medicine, National University Hospital, Singapore, Singapore
- 2Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
- 3National University Centre for Organ Transplantation, National University Hospital, Singapore, Singapore
Abstract
Despite advances in immunosuppression and histocompatibility assessment, late kidney allograft attrition remains an important challenge, with alloimmune injury a major cause of death-censored graft failure. More precise assessment of alloimmune risk could enable individualized immunosuppression and surveillance based on recipient risk. In this narrative review, we examine the evolution of histocompatibility assessment and the emergence of HLA molecular mismatch as a prognostic biomarker of alloimmunity. We review evidence linking molecular mismatch to de novo donor-specific antibody development, rejection and graft outcomes, and its interaction with immunosuppressive exposure. We critically evaluate potential applications to immunosuppression minimization, risk-adapted surveillance, and donor selection, while distinguishing prognostic validity from evidence for mismatch-guided intervention. Finally, we discuss methodological and biological limitations and emerging approaches integrating complementary molecular compatibility measures with functional and longitudinal biomarkers. Such multimodal strategies may ultimately enable more individualized assessment and management of alloimmune risk following kidney transplantation.
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BibTeX
@article{wong2026molecular,
title = {{HLA molecular mismatch – A step towards precision medicine in transplantation for individualized immune risk assessment and immunosuppression}},
author = {Christine Jia Yu Wong and Emmett Tsz Yeung Wong and Emmett Tsz Yeung Wong and Emmett Tsz Yeung Wong},
journal = {Frontiers in Medicine},
year = {2026},
month = oct,
doi = {10.3389/fmed.2026.1990225},
url = {https://doi.org/10.3389/fmed.2026.1990225},
note = {CC BY},
}
RIS
TY - JOUR
TI - HLA molecular mismatch – A step towards precision medicine in transplantation for individualized immune risk assessment and immunosuppression
AU - Christine Jia Yu Wong
AU - Emmett Tsz Yeung Wong
AU - Emmett Tsz Yeung Wong
AU - Emmett Tsz Yeung Wong
PY - 2026
DA - 2026/10/23
JO - Frontiers in Medicine
DO - 10.3389/fmed.2026.1990225
UR - https://doi.org/10.3389/fmed.2026.1990225
AB - Despite advances in immunosuppression and histocompatibility assessment, late kidney allograft attrition remains an important challenge, with alloimmune injury a major cause of death-censored graft failure. More precise assessment of alloimmune risk could enable individualized immunosuppression and surveillance based on recipient risk. In this narrative review, we examine the evolution of histocompatibility assessment and the emergence of HLA molecular mismatch as a prognostic biomarker of alloimmunity. We review evidence linking molecular mismatch to de novo donor-specific antibody development, rejection and graft outcomes, and its interaction with immunosuppressive exposure. We critically evaluate potential applications to immunosuppression minimization, risk-adapted surveillance, and donor selection, while distinguishing prognostic validity from evidence for mismatch-guided intervention. Finally, we discuss methodological and biological limitations and emerging approaches integrating complementary molecular compatibility measures with functional and longitudinal biomarkers. Such multimodal strategies may ultimately enable more individualized assessment and management of alloimmune risk following kidney transplantation.
SN - 2296-858X
ER -