title: Transplantation in the highly sensitized pediatric patient.
abstract: Sensitization against HLA antigens is a growing problem in the field of pediatric cardiac transplantation. Although surgical outcomes for congenital heart disease have improved over the decades, these successes have added to the growing list of sensitized patients who eventually may require transplantation.Cardiac transplantation survival has improved, but morbidity and mortality secondary to HLA antibodies hinder outcome. Aside from acute hemodynamic compromise, there is compelling evidence linking sensitization and AMR with the development of CAV, a major limiting factor affecting long-term graft survival. Clinical advances have improved our understanding of the roles of antibody type, CFAs and non-CFAs, and DSAs and non-DSAs. Therapeutic strategies target both the T- and B-cell lines. Combinations that include plasmapheresis, IVIG, cyclophosphamide, and rituximab have been used in clinical studies with variable success.Two newer agents show promise, targeting both ends of the antibody-mediated spectrum: Bortezomib depletes plasma cell populations, and eculizumab blocks the terminal effects of antibody action, thus preventing myocardial cell dysfunction and death. Despite numerous diagnostic and therapeutic advances, many questions remain about the best approaches.The role of HLA antibodies remains the central target of investigation.
authors.affiliation: From The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Chesney
authors.initials: C
authors.lastname: Castleberry
authors.affiliation: From The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Ryan
authors.affiliation: From The Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH. clifford.chin@cchmc.org.
authors.forename: Clifford
authors.initials: C
authors.lastname: Chin
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology; D000293:Adolescent; D000906:Antibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000627:therapeutic use; D006084:Graft Rejection / Q000276:immunology* / Q000517:prevention & control*; D006680:HLA Antigens / Q000276:immunology*; D016027:Heart Transplantation; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D010956:Plasmapheresis
chemical_list: D000017:ABO Blood-Group System; D000906:Antibodies; D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
keywords: HLA antigens; antibody mediated rejection; complement system proteins; heart transplantation