Matignon M, Tagnaouti M, Audard V, Dahan K, Lang P, Grimbert P
Department of Nephrology and Transplantation, Henri Mondor Hospital, Créteil, France.
Transplant Proc. 2007 Oct;39(8):2565-7. doi: 10.1016/j.transproceed.2007.08.038.
There is no optimal desensitization protocol for cadaveric renal transplant recipients who display high levels of donor-specific alloantibodies as defined by a positive T- or B-cell cytotoxic crossmatch. We used anti-CD20 monoclonal antibodies (Rituximab) to try to prevent antibody-mediated rejection in three crossmatch-positive renal transplants recipients (standard and sensitized techniques). The three patients received a first, second, or third cadaveric donor renal transplant. Patient one had an historical positive T- and B-cell cytotoxicity crossmatch: negative T- and B-cell cytotoxicity crossmatch at the day of transplantation. The panel reactive antibody (PRA) level was 100%. Patients 2 and 3 showed positive B-cell cytotoxicity crossmatches: historical and on the day of transplantation; PRA levels were 50% and 71%, respectively. All recipients were treated pretransplant with rituximab (375 mg/m(2)) and 4 days of intravenous immunoglobulin (0.5 g/kg body weight) per day posttransplant plus 5 days of thymoglobulin. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and prednisone. Antibody-mediated rejection occurred in all patients at day 6, day 10, or 8 months after renal transplantation. For patient 1, the rejection was not reversible and the graft was lost at day 15. Patient 2 had poor renal function with an MDRD estimate of glomerular filtration rate at 36 mL/min/1.73 m(2) at 18 months posttransplantation, and the graft of patient 3 was lost at 9 months posttransplantation due to resistant antibody-mediated rejection with thrombotic microangiopathy. In these three cases of crossmatch-positive patients, rituximab failed to prevent antibody-mediated rejection. Others studies will be needed to determine the place of rituximab in these patients.
对于T细胞或B细胞细胞毒性交叉配型呈阳性所定义的、显示高水平供体特异性同种抗体的尸体肾移植受者，尚无最佳脱敏方案。我们使用抗CD20单克隆抗体（利妥昔单抗），试图在3例交叉配型阳性的肾移植受者（标准技术和致敏技术）中预防抗体介导的排斥反应。这3例患者接受了首次、第二次或第三次尸体供体肾移植。患者1既往T细胞和B细胞细胞毒性交叉配型呈阳性：移植当天T细胞和B细胞细胞毒性交叉配型呈阴性。群体反应性抗体（PRA）水平为100%。患者2和3的B细胞细胞毒性交叉配型呈阳性：既往及移植当天均呈阳性；PRA水平分别为50%和71%。所有受者在移植前接受利妥昔单抗治疗（375 mg/m²），移植后每天接受4天静脉注射免疫球蛋白（0.5 g/kg体重）加5天抗胸腺细胞球蛋白治疗。维持免疫抑制包括他克莫司、霉酚酸酯和泼尼松。所有患者在肾移植后第6天、第10天或8个月均发生了抗体介导的排斥反应。对于患者1，排斥反应不可逆，移植肾在第15天丢失。患者2肾功能较差，移植后18个月时根据肾脏病饮食改良试验（MDRD）估算的肾小球滤过率为36 mL/min/1.73 m²，患者3的移植肾在移植后9个月因难治性抗体介导的排斥反应合并血栓性微血管病而丢失。在这3例交叉配型阳性的患者中，利妥昔单抗未能预防抗体介导的排斥反应。确定利妥昔单抗在这些患者中的地位还需要其他研究。
