Abstract
The development of de novo donor-specific antibodies is related to the poor matching of the human leukocyte antigen (HLA) between donor and recipient, which leads to dismal clinical outcomes and graft loss. However, new approaches that stratify the risks of long-term graft failure in solid organ transplantation have emerged, changing the paradigm of HLA compatibility. In addition, advances in software development have given rise to a new structurally based algorithm known as HLA Matchmaker, which determines compatibility at the epitope rather than the antigen level. Although this technique still has limitations, plenty of research maintains that this assessment represents a more complete and detailed definition of HLA compatibility. This review summarizes recent aspects of eplet mismatches, highlighting the most recent advances and future research directions.
Highlights
There have been many breakthroughs in solid organ transplantation, histocompatibility remains a challenge
Eplets have been described as functional epitopes as they include amino acids that can be recognized by anti-human leukocyte antigen (HLA) antibodies from among the whole amino acid structure that comprises an HLA epitope
In a 2014 study, Safavi et al performed a retrospective study of a cohort of 148 patients where they compared the relationship between de novo donor-specific antibodies (dnDSA) and the development of bronchiolitis obliterans syndrome (BOS), a clinical picture of progressive small-airway obstruction that leads to chronic allograft dysfunction, which is the primary cause of death beyond the first year of a lung transplant
Summary
There have been many breakthroughs in solid organ transplantation, histocompatibility remains a challenge. Poor HLA matching results in the formation of de novo donor-specific antibodies (dnDSA), which in turn lead to worse clinical outcomes and diminished graft survival [1]. Understanding how these antibodies (Abs) are developed can offer strategies to prevent their formation and could significantly improve long-term solid organ transplant results. Eplets have been described as functional epitopes as they include amino acids that can be recognized by anti-HLA antibodies from among the whole amino acid structure that comprises an HLA epitope This provides a higher resolution view of the antigen–antibody binding and a mechanistic explanation for the old idea of cross-reactive serological groups [2].
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