Achieving incompatible transplantation through desensitization: current perspectives and future directions

The application of life-saving transplantation is severely limited by the shortage of organs, and histoincompatibility. To increase transplant rates in sensitized patients, new protocols for HLA and blood type incompatible (ABOi) desensitization have emerged. These approaches require significant desensitization using intravenous immunoglobulin, rituximab and plasma exchange. In addition, the development of donor-specific antibody responses post transplant is the major cause of allograft failure with return to dialysis. This increases patient morbidity/mortality and cost. Immunotherapeutic agents used for desensitization evolved from drug development in oncology and autoimmune diseases. Currently, there is a renaissance in development of novel drugs likely to improve antibody reduction in transplantation. These include agents that inactivate IgG molecules, anticytokine antibodies, costimulatory molecule blockade, anticomplement agents and therapies aimed at the plasma cell.