title: Evolving paradigms for desensitization in managing broadly HLA sensitized transplant candidates.
abstract: The broadly human leukocyte antigen (HLA) sensitized patient awaiting organ transplantation remains a persistent and significant problem for transplant medicine. Sensitization occurs as a consequence of exposure to HLA antigens through pregnancy, blood and platelet transfusions, and previous transplants. Early experience with desensitization protocols coupled with improved diagnostics for donor-specific antibodies (DSAs) and renal pathology have greatly improved transplant rates and outcomes for patients once considered un-transplantable or at high risk for poor outcomes. More recent advances have occurred through implementation of a national allocation system requiring the entering of unacceptable antigens that reduces the rate of crossmatch positivity. Current desensitization therapies include high-dose intravenous immunoglobulin (IVIG), plasma exchange (PLEX) with low-dose IVIG, and IVIG combined with rituximab. Developing therapies include proteasome inhibitors aimed at plasma cells and modifiers of complement-mediated injury. Here we discuss the important advancements in desensitization including defining the risk for antibody-mediated rejection prior to transplantation and the evolution of therapies aimed at reducing the impact of antibody injury on allografts.
authors.affiliation: Comprehensive Transplant Center and HLA Laboratory, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. nancy.reinsmoen@cshs.org
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Reinsmoen
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lai
authors.forename: Ashley
authors.initials: A
authors.lastname: Vo
authors.forename: Stanley C
authors.initials: SC
authors.lastname: Jordan
mesh_terms: D000328:Adult; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology
chemical_list: D006680:HLA Antigens; D016756:Immunoglobulins, Intravenous