title: Successful treatment of severe ABO antibody-mediated rejection using bortezomib: a case report.
abstract: BACKGROUND
  Our program for ABO-incompatible renal transplantation includes antigen-specific immunoadsorption (extracorporeal columns with the A or B trisaccharides), rituximab, and standard maintenance immunosuppression. Anti-A or -B titers ≤ 8 in the indirect antiglobulin test (IAT) against panel A1 or B RBC are acceptable for transplantation.
  
  
  METHODS
  A previously healthy, 15-month-old girl was diagnosed with Wilms' tumor and proteinuria. Denys-Drash syndrome was confirmed. Bilateral nephrectomy was performed. At 3.5 years of age she received an ABO-incompatible renal transplant from her father (A1 to O). The anti-A titers before transplantation were low. She was treated preoperatively with rituximab, immunoadsorption, immunoglobulin and mycophenolate mofetil (MMF). The maintenance immunosuppression protocol included basiliximab, tacrolimus, MMF, and prednisolone. The initial postoperative course was uncomplicated with rapid normalization of serum creatinine. The anti-A titers started to increase on postoperative day 5 (8 NaCl/16 IAT). Despite daily immunoadsorptions the titers rose to 1024 NaCl/1024 IAT on day 9. Renal function deteriorated and hemodialysis was started. A renal biopsy on day 9 showed acute severe antibody-mediated rejection. Additional treatment with bortezomib was given and after 2 doses the titers started to decline, renal allograft function improved and hemodialysis was stopped. On day 21 posttransplant the titers went down, creatinine was 28 μmol/L, and no more immunoadsorptions were performed.
  
  
  CONCLUSIONS
  By using bortezomib, we were able to successfully reverse a severe ABO antibody-mediated rejection.
authors.affiliation: Department of Pediatrics, The Queen Silvia Children's Hospital, Göteborg, Sweden. susanne.westphal@vgregion.se
authors.forename: S
authors.initials: S
authors.lastname: Westphal
authors.forename: S
authors.initials: S
authors.lastname: Hansson
authors.forename: G
authors.initials: G
authors.lastname: Stelin
authors.forename: J
authors.initials: J
authors.lastname: Holgersson
authors.forename: L
authors.initials: L
authors.lastname: Mjörnstedt
authors.forename: S
authors.initials: S
authors.lastname: Friman
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D001897:Boronic Acids / Q000627:therapeutic use*; D000069286:Bortezomib; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D016030:Kidney Transplantation / Q000276:immunology*; D011719:Pyrazines / Q000627:therapeutic use*; D009396:Wilms Tumor / Q000601:surgery
chemical_list: D000017:ABO Blood-Group System; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib