Work

HLA molecular mismatch – A step towards precision medicine in transplantation for individualized immune risk assessment and immunosuppression

Year: 2026

Type: review

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.

Source: Frontiers in Medicine

DOI: 10.3389/fmed.2026.1990225

Authors: Christine Jia Yu Wong, Emmett Tsz Yeung Wong

Institutions: National University Hospital, National University of Singapore

Language: English

Topic: Renal Transplantation Outcomes and Treatments

Subfield: Transplantation

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801