Nordén Gunnela, Briggs David, Cockwell Paul, Lipkin Graham, Mjörnstedt Lars, Mölne Johan, Ready Andrew, Rydberg Lennart, Samuelsson Ola, Svalander Christian T, Breimer Michael E
Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg, Sweden.
Xenotransplantation. 2006 Mar;13(2):148-53. doi: 10.1111/j.1399-3089.2006.00280.x.
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.
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.
Blood group ABO-incompatible LD renal transplantation using A and B carbohydrate-specific IA and anti-CD20 mAbs has excellent graft survival and function.
血型ABO不相容的活体供肾（LD）肾移植可能提供重要的器官来源。我们报告了我们最初14例采用特异性抗A/B抗体（Ab）免疫吸附（IA）和抗CD20单克隆抗体（mAb）治疗的血型ABO不相容LD肾移植的结果。
受者血型为O型（n = 12）、A型（n = 1）和B型（n = 1）。供者为A1型（n = 2）、A2型（n = 3）、A2B型（n = 1）和B型（n = 8），且均为分泌型阳性。除1例受者外，所有受者的抗人白细胞抗原（HLA）抗体板反应性均为阴性。所有受者均预先接受3至6次IA治疗，使用A或B碳水化合物抗原柱，直至其抗A1/B红细胞抗体板间接抗球蛋白试验（IAT）滴度≤8。所有病例的补体依赖细胞毒交叉配型均为阴性。受者术前接受霉酚酸治疗，移植时开始使用类固醇/他克莫司。未行脾切除术。8例受者术前接受一剂抗CD20 mAb（利妥昔单抗，375 mg/m2），11例受者术后接受方案规定的IA治疗。
在最初的方案中，抗CD20 mAb仅用于接受A1移植物的受者。1例B移植物（HLA相同供者，抗体板反应性84%）在严重的抗B Ab介导的急性排斥反应中丢失。随后，方案包括对接受A1和B移植物的受者均使用抗CD20 mAb，并对所有受者进行术后方案规定的IA治疗。随后的10例移植物功能良好，总移植物存活率为13/14（观察期2至41个月）。1年时，平均血清肌酐为113 μmol/L（n = 8），平均肾小球滤过率为55 ml/min/1.73 m2（范围24至77）。在其余5例随访时间不足1年的病例中，随访2至9个月时平均血清肌酐为145 μmol/L。IA治疗前抗A/B滴度在2至32（NaCl技术）和16至512（IAT）范围内。14例受者共进行了90多次IA治疗，无任何明显副作用。受者抗A/B滴度在移植后恢复到IA治疗前水平或略低。10例患者进行了术后肾活检。在13例长期功能良好的患者中，1例患者在3个月时发生细胞性排斥反应（Banff IIB级），抗B滴度未升高。该排斥反应与他克莫司血药浓度低相关，且很容易被类固醇逆转。10例中的8例，肾小管周围毛细血管C4d染色阳性。
采用A和B碳水化合物特异性IA及抗CD20 mAb进行血型ABO不相容LD肾移植具有优异的移植物存活率和功能。
