Duneton Charlotte, Kwon Theresa, Dossier Claire, Baudouin Veronique, Fila Marc, Mariani-Kurkdijan Patricia, Nel Isabelle, Boyer Olivia, Hogan Julien
Pediatric Nephrology, Dialysis and Transplantation Department, Robert Debré University Hospital, APHP, Paris Cité University, Paris, France.
Université Paris Cité, INSERM U976, HIPI Unit: Human Immunology, Pathology, Immunotherapy, Paris, France.
Pediatr Nephrol. 2025 Feb;40(2):431-440. doi: 10.1007/s00467-024-06418-1. Epub 2024 Sep 19.
Neurological complications pose a significant threat in pediatric hemolytic and uremic syndrome (HUS) resulting from infections with Shiga toxin-producing Escherichia coli (STEC), with no established treatment. The involvement of complement activation in the pathogenesis of STEC-HUS is acknowledged, and eculizumab (ECZ), a terminal complement blocker, has been documented in several pediatric series with inconsistent results. Antibody-mediated mechanisms have also been suggested, with IgG-immunoadsorption (IgIA) showing promise in adults with neurological complications. We aimed to assess the benefit of combining IgIA with ECZ in pediatric patients with neurological STEC-HUS compared to patients treated with ECZ alone or supportive care.
Multicenter retrospective study conducted on pediatric patients (< 18 years) with neurological STEC-HUS treated with IgIA + ECZ or ECZ alone from 2010 to 2020 in France. A historical cohort treated with supportive care served as controls. Primary outcome included survival and neurological evaluation at 1-year follow-up (dichotomized as normal vs. abnormal).
A total of 42 children were included: 18 treated with IgIA + ECZ, 24 with ECZ alone, and 27 with supportive care. Although there was no significant difference in survival between groups, three deaths occurred in the control group in the acute phase, while none was reported in both the IgIA + ECZ and ECZ alone groups, despite presenting with more severe neurological symptoms for IgIA + ECZ patients. No significant association was found between treatment group and 1-year neurological evaluation after adjustment for age, sex, and initial neurological presentation.
Systematic association of IgIA + ECZ is not supported for all neurological STEC-HUS pediatric patients; potential rescue therapy for severe cases warrants consideration.
神经系统并发症对由产志贺毒素大肠杆菌（STEC）感染引起的小儿溶血尿毒综合征（HUS）构成重大威胁，目前尚无既定的治疗方法。补体激活参与STEC-HUS发病机制已得到公认，终末补体阻断剂依库珠单抗（ECZ）已在多个儿科系列研究中有所记载，但结果并不一致。也有人提出了抗体介导机制，免疫球蛋白G免疫吸附（IgIA）在患有神经系统并发症的成人中显示出前景。我们旨在评估与单独接受依库珠单抗治疗或支持性治疗的患者相比，IgIA联合依库珠单抗治疗对患有神经系统STEC-HUS的儿科患者的益处。
对2010年至2020年在法国接受IgIA联合依库珠单抗或单独依库珠单抗治疗的患有神经系统STEC-HUS的儿科患者（<18岁）进行多中心回顾性研究。以接受支持性治疗的历史队列作为对照。主要结局包括1年随访时的生存率和神经学评估（分为正常与异常）。
共纳入42名儿童：18名接受IgIA联合依库珠单抗治疗，24名仅接受依库珠单抗治疗，27名接受支持性治疗。尽管各组之间的生存率无显著差异，但对照组在急性期有3例死亡，而IgIA联合依库珠单抗组和仅接受依库珠单抗组均未报告死亡，尽管IgIA联合依库珠单抗组患者的神经症状更为严重。在对年龄、性别和初始神经学表现进行调整后，治疗组与1年神经学评估之间未发现显著关联。
不支持对所有患有神经系统STEC-HUS的儿科患者系统性联合使用IgIA联合依库珠单抗；对于重症病例，可能需要考虑采用挽救性治疗。
