title: Progress in Desensitization of the Highly HLA Sensitized Patient.
abstract: The presence of HLA antibodies remains a significant and often impenetrable barrier to kidney transplantation, leading to increased morbidity and mortality for patients remaining on long-term dialysis. In recent years, a number of new approaches have been developed to overcome these barriers. Intravenous immunoglobulin (IVIG) remains the lynchpin of HLA desensitization therapy and has been shown in a prospective, randomized, placebo-controlled trial to improve transplantation rates. In addition, IVIG used in low doses with plasma exchange is a reliable protocol for desensitization. Another significant advancement was the addition of rituximab (anti-B-cell therapy) to IVIG and plasma exchange-based desensitization. This approach has significantly improved rates of transplantation and outcomes. There is limited experience with bortezomib (anti-plasma cell therapy) and eculizumab (complement inhibition) for desensitization. However, recent data from a completed trial of eculizumab failed to show a significant benefit for prevention of antibody-mediated rejection compared with standard therapy plus placebo, and bortezomib produced inconsistent results. There is a growing interest in developing new therapeutic agents for desensitization. Newer approaches that address antibody reduction with B-cell depletion are discussed.
authors.affiliation: Transplant Immunotherapy Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California. Electronic address: stan.jordan@cshs.org.
authors.forename: S C
authors.initials: SC
authors.lastname: Jordan
authors.affiliation: Transplant Immunotherapy Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: J
authors.initials: J
authors.lastname: Choi
authors.affiliation: Transplant Immunotherapy Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: J
authors.initials: J
authors.lastname: Kahwaji
authors.affiliation: Transplant Immunotherapy Program, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, California.
authors.forename: A
authors.initials: A
authors.lastname: Vo
mesh_terms: D003888:Desensitization, Immunologic / Q000379:methods*; D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D016030:Kidney Transplantation; D010951:Plasma Exchange; D000069283:Rituximab / Q000627:therapeutic use
chemical_list: D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous; D000069283:Rituximab