Allosensitization in heart transplantation: implications and management strategies

The detection of anti-human leukocyte antigen (HLA) donor-specific antibodies has been associated with a variety of clinical syndromes that determine short-term and long-term outcomes of cardiac transplant recipients, including an increased incidence of early and more severe allograft rejection and cardiac allograft vasculopathy. Recent surveys indicate marked heterogeneity in clinical protocols for detection and management of sensitization in heart transplantation. The commonly performed complement-dependent cytotoxicity assay is insensitive compared with newer methods such as flow cytometry for antibody screening. The imperative exists to create strategies that can decrease the level of sensitization and increase the likelihood for a negative crossmatch. In this effort, several strategies have been suggested, including administration of intravenous immunoglobulin, apheresis, and combination therapies using potent immunosuppression, particularly with cyclophosphamide. The future of managing allosensitization may be in induction of a chimeric state to allow graft tolerance.