title: ABO-incompatible live donor renal transplantation using blood group A/B carbohydrate antigen immunoadsorption and anti-CD20 antibody treatment.
abstract: BACKGROUND
  Blood group ABO-incompatible live donor (LD) renal transplantation may provide a significant source of organs. We report the results of our first 14 cases of ABO-incompatible LD renal transplantation using specific anti-A/B antibody (Ab) immunoadsorption (IA) and anti-CD20 monoclonal Ab (mAb) treatment. PATIENTS AND TREATMENT PROTOCOL: Recipients were blood group O (n = 12), A (n = 1) and B (n = 1). Donors were A1 (n = 2), A2 (n = 3), A2B (n = 1) and B (n = 8), and all were secretor positive. Anti-human leukocyte antigen (HLA) Ab panel reactivity was negative in all recipients except one. All recipients were pre-treated with 3 to 6 IA sessions, using A or B carbohydrate antigen columns, until their anti-A1/B RBC panel indirect antiglobulin test (IAT) titers were < or =8. CDC crossmatch was negative in all cases. Recipients received preoperative mycophenolic acid, and steroids/tacrolimus were started at transplantation. No splenectomy was performed. Eight recipients received one dose of anti-CD20 mAb (rituximab, 375 mg/m2) pre-operatively and 11 recipients had postoperative protocol IA.
  
  
  RESULTS
  In the initial protocol, anti-CD20 mAbs were used only for recipients receiving A1 grafts. One B graft (HLA-identical donor, 84% panel reactivity) was lost in a severe anti-B Ab-mediated acute rejection. Subsequently, the protocol included anti-CD20 for recipients of both A1 and B grafts and postoperative protocol IA to all recipients. The subsequent 10 grafts had excellent function, giving a total graft survival of 13/14 (observation range 2 to 41 months). At 1 yr, mean serum creatinine was 113 micromol/l (n = 8) and mean glomerular filtration rate was 55 ml/min/1.73 m2 (range 24 to 77). In the remaining five cases, with less than 1 yr follow up, mean serum creatinine was 145 micromol/l at 2 to 9 months follow up. Pre-IA anti-A/B titers were in the range of 2 to 32 (NaCl technique) and 16 to 512 (IAT). More than 90 IA sessions were performed in 14 recipients without any significant side effects. Recipient anti-A/B titers returned after transplantation to pre-IA levels or slightly lower. Postoperative renal biopsies were performed in 10 patients. In the 13 patients with long-term function, one patient experienced cellular rejection (Banff IIB) at 3 months without anti-B titer rise. This rejection was concomitant with low tacrolimus plasma levels and was easily reversed by steroids. In 8 of 10 cases, C4d staining was positive in peritubular capillaries.
  
  
  CONCLUSIONS
  Blood group ABO-incompatible LD renal transplantation using A and B carbohydrate-specific IA and anti-CD20 mAbs has excellent graft survival and function.
authors.affiliation: Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Gunnela
authors.initials: G
authors.lastname: Nordén
authors.forename: David
authors.initials: D
authors.lastname: Briggs
authors.forename: Paul
authors.initials: P
authors.lastname: Cockwell
authors.forename: Graham
authors.initials: G
authors.lastname: Lipkin
authors.forename: Lars
authors.initials: L
authors.lastname: Mjörnstedt
authors.forename: Johan
authors.initials: J
authors.lastname: Mölne
authors.forename: Andrew
authors.initials: A
authors.lastname: Ready
authors.forename: Lennart
authors.initials: L
authors.lastname: Rydberg
authors.forename: Ola
authors.initials: O
authors.lastname: Samuelsson
authors.forename: Christian T
authors.initials: CT
authors.lastname: Svalander
authors.forename: Michael E
authors.initials: ME
authors.lastname: Breimer
mesh_terms: D000017:ABO Blood-Group System / Q000276:immunology*; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D000941:Antigens / Q000276:immunology*; D018951:Antigens, CD20 / Q000276:immunology*; D001706:Biopsy; D001787:Blood Group Incompatibility / Q000276:immunology; D002241:Carbohydrates / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology* / Q000473:pathology; D019520:Living Donors; D008875:Middle Aged; D000069283:Rituximab; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000941:Antigens; D018951:Antigens, CD20; D002241:Carbohydrates; D000069283:Rituximab