title: Bortezomib as an adjuvant to conventional therapy in the treatment of antibody mediated rejection (AMR): the full spectrum.
abstract: Antibody-mediated rejection (AMR) is a well-known complication of kidney transplantation. Its incidence is higher in HLA and ABO incompatible transplant recipients and in patients who develop de novo HLA antibodies. Different clinical and histological phenotypes of HLA-related AMR have been described with variable responses to conventional AMR treatment (Plasmapheresis, IVIG, thymoglobulin (ATG), and anti-CD20 antibodies). Regardless of the phenotype, once the HLA primed B cells have differentiated into antibody producing long-lived plasma cells, they become less vulnerable to conventional AMR treatment. Bortezomib (Velcade) is a proteasome inhibitor approved by the FDA for the treatment of multiple myeloma. It targets mature plasma cells, and hence it is intriguing to study its role in the suppression of long-lived plasma cells. Several previous reports have suggested effectiveness of Bortezomib in the treatment of AMR. We report our experience with Bortezomib as an adjuvant to conventional therapy in five distinct phenotypes of AMR: early acute AMR in the context of desensitization; subclinical acute AMR in the context of desensitization; late acute AMR due to de novo HLA antibody; late ACR and acute AMR due to de novo HLA antibody and chronic AMR due to de novo HLA antibody.
authors.affiliation: King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
authors.forename: K
authors.initials: K
authors.lastname: Al Meshari
authors.forename: A
authors.initials: A
authors.lastname: Pall
authors.forename: H
authors.initials: H
authors.lastname: Elgamal
authors.forename: F
authors.initials: F
authors.lastname: Alzayer
authors.forename: M
authors.initials: M
authors.lastname: Altalhi
mesh_terms: D000208:Acute Disease; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D056724:Immunity, Humoral / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D011480:Protease Inhibitors / Q000627:therapeutic use*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D012529:Saudi Arabia; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D001897:Boronic Acids; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex