Habbig Sandra, Debiec Hanna, Chedik Malha, Stippel Dirk L, Erger Florian, Lourenço Alexia, Liebau Max C, Ronco Pierre
Department of Pediatrics, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany; Center for Family Health, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany; Center for Rare Diseases, University Hospital Cologne and Faculty of Medicine, University of Cologne, Cologne, Germany.
Sorbonne Université, Paris, France; Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S 1155, Paris, France.
Kidney Int. 2025 Aug;108(2):321-327. doi: 10.1016/j.kint.2025.04.015. Epub 2025 May 16.
Disease recurrence after kidney transplantation (KTx) remains a major challenge in patients with primary focal segmental glomerulosclerosis (pFSGS). Antibodies targeting the slit diaphragm protein nephrin have been identified in patients with early disease recurrence. Here, we describe monitoring and effective pre-transplant elimination of anti-nephrin antibodies in an adolescent with pFSGS prior to living-donor KTx.
Anti-nephrin antibodies were assessed in pre- and post-transplant serum samples by ELISA, Western blot and immunoprecipitation using three different nephrin proteins.
Pre-transplant treatment including rituximab and repetitive therapeutic plasma exchanges resulted in effective and sustainable reduction of anti-nephrin antibodies. Allograft function has remained excellent without albuminuria over a follow-up of more than one year. Further analysis showed that the antibodies were cross-reactive with NEPH3 (filtrin), another key slit diaphragm protein.
Monitoring and pre-transplant elimination of anti-slit diaphragm antibodies may become a standard, personalized approach in patients with pFSGS requiring KTx.
对于原发性局灶节段性肾小球硬化（pFSGS）患者，肾移植（KTx）后疾病复发仍然是一个重大挑战。在疾病早期复发的患者中已发现靶向裂孔隔膜蛋白nephrin的抗体。在此，我们描述了在一名患有pFSGS的青少年活体供肾KTx术前对抗nephrin抗体的监测及有效的术前清除。
通过ELISA、Western印迹法以及使用三种不同的nephrin蛋白进行免疫沉淀，对移植前后的血清样本中的抗nephrin抗体进行评估。
包括利妥昔单抗和重复治疗性血浆置换的术前治疗有效且持续地降低了抗nephrin抗体。在超过一年的随访中，移植肾功能一直良好，无蛋白尿。进一步分析表明，这些抗体与另一种关键的裂孔隔膜蛋白NEPH3（滤过素）存在交叉反应。
对于需要进行KTx的pFSGS患者，监测和术前清除抗裂孔隔膜抗体可能会成为一种标准的个性化方法。
