title: Proteasome inhibition with bortezomib: an effective therapy for severe antibody mediated rejection after renal transplantation.
abstract: Antibody-mediated rejection (AMR) following renal transplantation is  less responsive to conventional anti-rejection  therapies. Plasmapheresis (PP), intravenous  immunoglobulin (IVIg), rabbit antithymocyte  globulin (rATG) and rituximab deplete  immature B-cells but not mature plasma  cells. The proteasome inhibitor bortezomib  has activity against mature plasma cell, the  source of damaging donor-specific antibody  (DSA).We present the successful use of bortezomib  in 2 patients who developed AMR  following kidney transplantation. The first  patient was a 54-year-old white female who  received living-unrelated kidney transplantation  from her husband. She developed severe  AMR early after transplantation with rising  DSA titers consistent with an anamnestic  immune response by memory cells to the  donor antigens. Renal function deteriorated  despite treatment with pulse methylprednisolone  (MP), PP and IVIg. After initiation  of therapy with bortezomib, DSA titers became  negative and serum creatinine returned  to baseline with histological resolution of  AMR. The second patient was a 19-year-old  white male who received deceased donor  kidney transplantation and developed AMR  within 2 weeks, refractory to therapy with  pulse MP, PP and IVIg with rising DSA.  Bortezomib use resulted in disappearance of  DSA and renal function improvement. Both  patients tolerated the treatment well with  stable renal function at last follow-up. The  novel mechanisms of action and preliminary  results with bortezomib are encouraging, but  require larger studies and longer follow-up.
authors.affiliation: Divisions of Nephrology and Hypertension, Allegheny General Hospital, Pittsburgh, PA, USA. ksureshk@wpahs.org
authors.forename: Kalathil K
authors.initials: KK
authors.lastname: Sureshkumar
authors.forename: Sabiha M
authors.initials: SM
authors.lastname: Hussain
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Marcus
authors.forename: Tina Y
authors.initials: TY
authors.lastname: Ko
authors.forename: Akhtar S
authors.initials: AS
authors.lastname: Khan
authors.forename: Kusum
authors.initials: K
authors.lastname: Tom
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Vivas
authors.forename: George
authors.initials: G
authors.lastname: Parris
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Jasnosz
authors.forename: Ngoc L
authors.initials: NL
authors.lastname: Thai
mesh_terms: D000328:Adult; D001706:Biopsy; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D006801:Humans; D007518:Isoantibodies / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000601:surgery*; 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*; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001897:Boronic Acids; D007518:Isoantibodies; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D000069286:Bortezomib; D046988:Proteasome Endopeptidase Complex