Department of Pediatrics I, University Children's Hospital, Heidelberg, Germany.
Transpl Int. 2012 Nov;25(11):1165-73. doi: 10.1111/j.1432-2277.2012.01544.x. Epub 2012 Aug 17.
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 m² during 6 months prior to AHT to 2.1 ml/min/1.73 m² (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.
慢性抗体介导的排斥反应（AMR）是导致晚期肾移植失败的主要原因。然而，目前对此病症尚无既定的治疗方法。我们报告了一项针对 20 名儿科肾移植受者进行的、包含高剂量静脉注射免疫球蛋白 G（IVIG）和利妥昔单抗的抗体液治疗（AHT）的前瞻性试验研究结果。供体特异性 HLA 抗体（HLA DSA）采用基于 Luminex 的珠阵列技术进行定量。eGFR 从 AHT 前 6 个月的 7.6 ml/min/1.73 m²显著下降至 AHT 后 6 个月的 2.1 ml/min/1.73 m²（P = 0.0013）。14 名患者（70%）有反应：9 名无移植肾小球病（PTC）患者（100%）和 11 名有 PTC 患者中的 5 名（45%）（P = 0.014）。PTC 中的 C4d 阳性率从基线活检的 40 ± 18.5%下降至随访活检的 11.6 ± 12.2%（P = 0.002）。9 名活检中有 4 名（44%）的 C4d 染色转为阴性。在 2 年的随访中，与 AHT 前相比，每个 6 个月期的 eGFR 中位丢失仍显著降低。AHT 后 12 个月，I 类 DSA 下降 61%（p = 0.044），II 类 DSA 下降 63%（p = 0.033）。IVIG 和利妥昔单抗联合 AHT 可显著降低或稳定儿科慢性 AMR 患者的移植肾功能进行性丧失，在 2 年的观察期内，其机制可能是通过降低循环 DSA 和减少肾内补体激活。
