title: Clinical and investigational use of proteasome inhibitors for transplant rejection.
abstract: BACKGROUND
  The presence of donor-specific anti-human leukocyte antigen (HLA) antibodies (DSA) in patients experiencing acute cellular rejection and antibody-mediated rejection (AMR) is associated with poor renal allograft survival in kidney transplant recipients. Traditional therapies for AMR provide variable results, and do not deplete the cellular source of antibody production, that is, the plasma cell.
  
  
  METHODS
  Physiologic effects of proteasome inhibitors (PIs) are reviewed in the context of recent clinical reports of PI therapy in solid organ transplantation for AMR and desensitization.
  
  
  CONCLUSIONS
  PI-based therapy is a novel approach for treating AMR that is being employed with increasing frequency in transplantation. Initial reports of PI-based regimens for treating AMR have demonstrated the ability of bortezomib to significantly reduce DSA levels and improve histology and allograft function. Use of PI agents have recently been evaluated in a large multicenter collaborative consisting of over 100 solid organ transplant recipients treated with a common PI-based regimen. Increasing experience with PI-based regimens for AMR have indicated that PI therapy (similar to other AMR therapies) provides excellent results in early AMR, with late AMR demonstrating a greater degree of therapeutic resistance. A substantial number of strategies exist for enhancement of therapeutic results with PI therapy for AMR.
authors.affiliation: University of Cincinnati College of Medicine, Division of Nephrology, Department of Internal Medicine, Cincinnati, OH 45267 0558, USA.
authors.forename: Basma
authors.initials: B
authors.lastname: Sadaka
authors.forename: Rita R
authors.initials: RR
authors.lastname: Alloway
authors.forename: E Steve
authors.initials: ES
authors.lastname: Woodle
mesh_terms: D000818:Animals; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use; D000069286:Bortezomib; D006084:Graft Rejection / Q000188:drug therapy* / Q000201:enzymology; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib