Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
Transplantation. 2010 May 15;89(9):1095-102. doi: 10.1097/TP.0b013e3181d21e7f.
BACKGROUND.: We have shown that high-dose intravenous immune globulin (IVIG; 2 g/kg x2 doses)+rituximab (1 g x2 doses) was effective in lowering anti-human leukocyte antigen (HLA) antibodies and improving rates of transplantation. The aim of this report was to evaluate the efficacy of IVIG+rituximab on reduction of anti-HLA antibodies to a level that was permissive for living donor (LD) or deceased donor (DD) transplantation without incurring the risk of antibody-mediated rejection and immediate graft loss. METHODS.: From July 2006 to February 2009, 76 HLA-sensitized (HS) patients who met strict sensitization criteria received kidney transplants after desensitization using IVIG 2 g/kg (days 1 and 30)+rituximab (1 g, day 15). Parameters evaluated included rates of transplantation, previous transplants, panel reactive antibodies, donor specific antibody, crossmatches (CMXs), patient and graft survival, acute rejection, serum creatinines, and infections. RESULTS.: Seventy-six HS CMX treated patients (31 LD/45 DD) were transplanted. For LD and DD recipients, significant reductions were seen in T-cell flow cytometry CMXs from pretreatment (T cell 183.5+/-98.4 mean channel shifts (MCS) for LD and 162.8+/-41 MCS for DD) to time of transplant (T cell 68.2+/-58 MCS for LD [P<0.00006] and 125+/-49 for DD [P=0.05]), respectively. Time on wait list for DD recipients was reduced from 95+/-46 months to 4.2+/-4.5 months after treatment. Twenty-eight patients (37%) experienced acute rejection (29% C4d/8% C4d). Patient and graft survival up to 24 months was 95% and 84%, respectively. The mean serum creatinines, at 12 and 24 months were 1.5+/-1.1 and 1.3+/-0.3 mg/dL, respectively. Viral infections were seen in six patients. CONCLUSIONS.: IVIG and rituximab seems to offer significant benefits in reduction of anti-HLA antibodies allowing improved rates of transplantation for HS patients, especially those awaiting DD, with acceptable antibody-mediated rejection and survival rates at 24 months.
我们已经证明，高剂量静脉注射免疫球蛋白（IVIG；2 g/kg x2 剂量）+利妥昔单抗（1 g x2 剂量）可有效降低抗人白细胞抗原（HLA）抗体并提高移植率。本报告的目的是评估 IVIG+利妥昔单抗降低 HLA 抗体水平以允许接受活体供体（LD）或已故供体（DD）移植的效果，而不会产生抗体介导的排斥反应和即时移植物丢失的风险。方法：自 2006 年 7 月至 2009 年 2 月，76 名符合严格致敏标准的 HLA 致敏（HS）患者在接受 IVIG 2 g/kg（第 1 天和第 30 天）+利妥昔单抗（1 g，第 15 天）脱敏后接受了肾移植。评估的参数包括移植率、既往移植、面板反应性抗体、供体特异性抗体、交叉配型（CMX）、患者和移植物存活率、急性排斥反应、血清肌酐和感染。结果：76 名 HS CMX 治疗患者（31 名 LD/45 名 DD）接受了移植。对于 LD 和 DD 受者，T 细胞流式细胞术 CMX 从预处理（LD 为 T 细胞 183.5+/-98.4 平均通道移位（MCS），DD 为 162.8+/-41 MCS）到移植时（LD 为 T 细胞 68.2+/-58 MCS [P<0.00006]和 DD 为 125+/-49 MCS [P=0.05]）分别显著降低。DD 受者的等待名单时间从 95+/-46 个月减少到治疗后的 4.2+/-4.5 个月。28 名患者（37%）发生急性排斥反应（29% C4d/8% C4d）。截至 24 个月时，患者和移植物存活率分别为 95%和 84%。12 个月和 24 个月时的平均血清肌酐分别为 1.5+/-1.1 和 1.3+/-0.3 mg/dL。6 名患者出现病毒感染。结论：IVIG 和利妥昔单抗似乎在降低抗 HLA 抗体方面具有显著优势，可提高 HS 患者，特别是等待 DD 的患者的移植率，同时具有可接受的抗体介导的排斥反应和 24 个月时的存活率。
