IVIG and rituximab for treatment of chronic antibody-mediated rejection: a prospective study in paediatric renal transplantation with a 2-year follow-up
IVIG and rituximab for treatment of chronic antibody-mediated rejection: a prospective study in paediatric renal transplantation with a 2-year follow-up
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DOI：
10.1111/j.1432-2277.2012.01544.x
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发表时间：
2012-11-01
影响因子：
3.1
通讯作者：
Toenshoff, Burkhard
中科院分区：
文献类型：
--
作者：
Billing, Heiko;Rieger, Susanne;Toenshoff, Burkhard
慢性抗体介导的排斥反应（AMR）是导致移植肾晚期失功的主要原因。然而，对于这种情况没有既定的治疗方法。我们报告了一项前瞻性试验研究的结果，抗体液治疗（AHT）组成的大剂量静脉注射免疫球蛋白G（IVIG）和利妥昔单抗在20名儿童肾移植受者。通过基于Luminex的微珠阵列技术定量供体特异性HLA抗体（HLA DSA）。eGFR损失从AHT前6个月的7.6 ml/min/1.73 m（2）显着下降至AHT后6个月的2.1 ml/min/1.73 m（2）（P = 0.0013）。14名患者（70%）有反应：9名患者（100%）无移植肾小球病，11名患者（45%）有移植肾小球病（P = 0.014）。PTC的C4d阳性率从索引活检的40 +/- 18.5%降至随访活检的11.6 +/- 12.2%（P = 0.002）。9例活检中有4例（44%）C4d染色转为阴性。在2年的随访期间，与AHT之前相比，四个6个月期间的eGFR中位损失均显著降低。干预后12个月，AHT的I级DSA下降了61%（p = 0.044），II级DSA下降了63%（p = 0.033）。在2年的观察期内，AHT联合IVIG和利妥昔单抗显著降低或稳定了慢性AMR儿科患者的移植功能进行性丧失，这显然是通过降低循环DSA和减少肾内补体激活实现的。
Chronic antibody-mediated rejection (AMR) is the major cause of late renal allograft loss. There is, however, no established treatment for this condition. We report the results of a prospective pilot study on an antihumoral therapy (AHT) consisting of high-dose intravenous immunoglobulin G (IVIG) and rituximab in 20 paediatric renal transplant recipients. Donor-specific HLA antibodies (HLA DSA) were quantified by Luminex-based bead array technology. Loss of eGFR decreased significantly from 7.6 ml/min/1.73 m(2) during 6 months prior to AHT to 2.1 ml/min/1.73 m(2) (P = 0.0013) during 6 months after AHT. Fourteen patients (70%) responded: nine of nine patients (100%) without and five of 11 (45%) with transplant glomerulopathy (P = 0.014). C4d positivity in PTC decreased from 40 +/- 18.5% in the index biopsy to 11.6 +/- 12.2% (P = 0.002) in the follow-up biopsy. In four of nine biopsies (44%) C4d staining turned negative. During 2 years of follow-up, the median loss of eGFR in each of the four 6-month periods remained significantly lower compared with prior to AHT. Class I DSA declined in response to AHT by 61% (p = 0.044), class II DSA by 63% (p = 0.033) 12 months after intervention. AHT with IVIG and rituximab significantly reduces or stabilizes the progressive loss of transplant function in paediatric patients with chronic AMR over an observation period of 2 years, apparently by lowering circulating DSA and reducing intrarenal complement activation.