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A perspective on xenograft rejection and accommodation

J L Platt1

  • 1Duke University Medical Center, Durham, NC 27710.

Immunological Reviews
|October 1, 1994
PubMed
Summary

Xenotransplantation faces challenges from xenoreactive antibodies and complement activation, leading to graft rejection. Strategies to overcome these barriers are advancing clinical xenotransplantation possibilities.

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Area of Science:

  • Transplantation immunology
  • Organ transplantation research

Background:

  • Increasing interest in xenotransplantation due to organ shortages.
  • Progress in understanding xenograft rejection mechanisms, particularly antibody-mediated events.

Purpose of the Study:

  • Characterize xenoreactive antibodies and their role in xenograft rejection.
  • Investigate effector mechanisms of complement activation.
  • Explore strategies to overcome rejection for clinical xenotransplantation.

Main Methods:

  • Characterization of xenoreactive antibodies (IgM) recognizing porcine integrins.
  • Analysis of complement activation pathways (classical pathway).
  • Identification of effector mechanisms including endothelial cell damage and thrombosis.

Main Results:

  • Xenoreactive antibodies target alpha Gal residues on porcine glycoproteins.
  • Complement activation leads to endothelial cell damage, procoagulant changes, and neutrophil adhesion.
  • Hyperacute rejection can be prevented, but acute vascular rejection and accommodation phenomena are observed.

Conclusions:

  • Understanding xenoreactive antibodies and complement is crucial for xenotransplantation.
  • Therapeutic strategies like immunoabsorbants and transgenic animals show promise.
  • Further research into accommodation mechanisms is needed for clinical success.

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