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Predicting permissible Human Leukocyte Antigen (HLA) mismatches is crucial for transplant success. This review covers HLA-directed alloreactivity and tools to predict direct and indirect immune responses, improving donor-recipient matching.

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Area of Science:

  • Immunology
  • Transplantation Science
  • Genetics

Background:

  • Human Leukocyte Antigen (HLA) mismatching is a primary cause of severe complications in solid-organ and hematopoietic stem-cell transplantation.
  • Alloreactive responses, including direct and indirect T-cell recognition of mismatched HLA, drive post-transplant adverse events.
  • The clinical impact of HLA mismatches varies significantly, with some being well-tolerated and others causing severe alloreactivity.

Purpose of the Study:

  • To provide a comprehensive overview of current knowledge on HLA-directed alloreactivity.
  • To review in vitro and in silico tools developed for predicting HLA mismatch permissibility.
  • To aid in selecting donor-recipient combinations that minimize deleterious host-versus-graft and graft-versus-host responses.

Main Methods:

  • Review of existing literature on HLA immunogenicity and alloreactivity.
  • Analysis of in vitro assays used to assess HLA-specific immune responses.
  • Evaluation of in silico computational tools for predicting HLA mismatch outcomes.

Main Results:

  • HLA mismatch immunogenicity is variable, influencing transplant outcomes.
  • Direct and indirect alloreactive pathways contribute to post-transplant complications.
  • Predictive tools aim to differentiate permissible from non-permissible HLA mismatches.

Conclusions:

  • Accurate prediction of HLA mismatch permissibility is essential for optimizing transplantation outcomes.
  • A combination of in vitro and in silico methods offers promise for predicting alloreactivity.
  • Improved donor-recipient matching based on HLA compatibility can reduce transplant-related morbidity and mortality.