Therapeutic strategies in management of the highly HLA-sensitized and ABO-incompatible transplant recipients.

Intravenous immunoglobulin (IVIG) products are derived from pooled human plasma and have been used for the treatment of primary immunodeficiency disorders for more than 24 years. Shortly after their introduction, IVIG products were found to be effective in the treatment of autoimmune and inflammatory disorders. Rituximab (anti-CD20, anti-B-cell monoclonal antibody) has also shown efficacy in the treatment of autoimmune and inflammatory disorders. We have recently described a beneficial effect of the combination of IVIG + rituximab on the reduction of anti-human leukocyte antigen (HLA) antibodies with subsequent improvement in rates of transplantation for highly HLA-sensitized patients as well as a potent anti-inflammatory effect that is beneficial in the treatment of antibody-mediated rejection. These advancements have enabled patients previously considered poor or unreasonable candidates for transplantation to receive a successful transplant. Alternative approaches to IVIG/rituximab-based desensitization include the addition of plasmapheresis and possible splenectomy. Furthermore, new advancements in detecting donor-specific anti-body and assessment of antibody-mediated injury to allografts (C4d staining) allow for early detection of antibody-mediated rejection and early implementation of IVIG/rituximab therapy to prevent allograft loss.