title: The state of therapy for removal of alloantibody producing plasma cells in transplantation.
abstract: The current evidence clearly points towards donor specific alloantibody as a major cause of allograft loss. In order to mitigate allograft loss due to antibodies, treating the source of antibody production, the plasma cell is essential. Therapies that lack effect on the terminally differentiated (long-lived) plasma cell, such as rituximab, intravenous immune globulin and, plasmapheresis were the therapies used prior to 2007. In studies, their ability to remove antibody was found to be incomplete and/or cost prohibitive. In 2007, a proteasome inhibitor, bortezomib, was used for the first time in transplant due to its ability to deplete plasma cells. Through multiple case reports it has demonstrated consistent success in DSA reduction and removal, with only a few reports of failure to date. This review discusses the plasma cell, the alloantibody, and the current data supporting proteasome inhibitor use in transplant.
authors.affiliation: One Lambda Inc., Canoga Park, CA, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Everly
authors.forename: Paul I
authors.initials: PI
authors.lastname: Terasaki
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007518:Isoantibodies / Q000096:biosynthesis*; D016030:Kidney Transplantation / Q000276:immunology; D051379:Mice; D010950:Plasma Cells / Q000187:drug effects* / Q000276:immunology; D011480:Protease Inhibitors / Q000627:therapeutic use*; D011719:Pyrazines / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D007518:Isoantibodies; D011480:Protease Inhibitors; D011719:Pyrazines; D000069286:Bortezomib