IBMS Congress

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Incompatible solid organ transplants

Session 2

Immunology

The dogma that preformed HLA specific antibodies cause hyperactute rejection (HAR) of an organ transplant is well founded. 

Most transplanted solid organs are susceptible to donor specific antibodies, although livers are relatively protected from HAR. In the late 1960s the introduction of a pretransplant lymphocyte cytotoxicity crossmatch almost completely eliminated this form of graft loss. While antigen avoidance allows transplantation of many sensitised patients there are still many denied access to an antibody compatible donor. In the UK about 250 living donor transplants per year are stopped because of antibody incompatibility and for these we require strategies to transplant in the presence of HLA specific antibodies (ie antibody incompatible transplantation).

One approach might be to wait for antibody levels to diminish naturally to below detection in a crossmatch but for many highly sensitised patients their antibodies can persist at high levels for years or decades with the prediction of death before transplantation might be possible. Antibody removal (eg by plasmapharesis) can accelerate significant antibody reduction to a matter of hours or days. Once a negative crossmatch has been reached transplantation must follow quickly so this is mostly use in live donor transplantation.

A third strategy might be to consider the relative pathogenicity of a donor specific antibodies. Both the properties of the antibodies (eg ability to activate complement) and those of the target antigen (eg expression pattern of the different HLA isotypes A, B, C, DR, DQ, and DP) might be exploited to allow transplantation across antibody barriers. Finally, complement inhibitors are beginning to show some potential in cases where antibody reduction has not been possible.

One factor that has helped the recent growth of successful antibody incompatible transplantation is the new generation of antibody assays using antigen coated beads. Rapid testing and reporting in real time has allowed monitoring of relative antibody levels in a way that is not previously possible.  Bead assays have also given us a tool which we can better define antibody specificity and analyse the properties of these antibodies. A better understanding of HLA specific antibodies should increase the safety of this procedure and widen access to this form of treatment.