Dataset related to the article "C3d-targeted complement inhibitors to correct complement dysregulation in aHUS patients"

The .pdf file contains raw data related to the article C3d-targeted complement inhibitors to correct complement dysregulation in aHUS patients. Frontiers in Immunology. 2025; 16: 1620996. doi: 10.3389/fimmu.2025.1620996. Abstract Atypical hemolytic uremic syndrome (aHUS) is a rare and severe thrombotic microangiopathy caused by genetic or acquired abnormalities leading to activation of the complement alternative pathway on cell surfaces. This process leads to endothelial dysfunction and microvascular thrombosis. The introduction of anti-C5 antibodies has dramatically improved aHUS prognosis; however, these treatments require regular intravenous infusions and block systemic complement activity, exposing the patient to risk of infections. Recently complement inhibitors have been developed to selectively bind injury-associated target molecules, thereby concentrating the drug at specific cellular or tissue sites while preserving systemic complement function. This study evaluated the local complement inhibitory activity of new molecules that exploit the natural localization of C3d at complement activation sites on cells: namely the anti-C3d monoclonal antibody 3d8b conjugated with the first 10 or 17 short consensus repeats (SCRs) of complement receptor 1 (CR11-10 and CR11-17, respectively) or the first 5 SCRs of complement factor H (FH1-5). To this purpose we tested their capability to block C3 deposition and C5b-9 formation on microvascular endothelial cells (HMEC-1) exposed to serum from patients with aHUS. We also assessed their ability to prevent loss of anti-thrombogenic properties in HMEC-1 pre-exposed to aHUS serum and then perfused with control blood. We demonstrate that anti-C3d-antibody conjugated with CR11-10, or CR11-17, or FH1-5 effectively prevented aHUS serum-induced complement activation on HMEC-1, outperforming their non-targeted soluble counterparts. The efficacy of C3 convertase inhibition varied depending on the complement inhibitory component (CR11-17 > CR11-10 > FH1-5). However, all the inhibitors successfully blocked C5 convertase activity and eliminated the pro-thrombogenic effects of aHUS patients' serum. These findings support the potential of tissue-targeted complement inhibition as a novel, non-systemic therapeutic strategy for aHUS and other diseases characterized by localized complement dysregulation.本PDF文件包含与论文《靶向C3d的补体抑制剂用于纠正非典型溶血尿毒综合征患者的补体失调》相关的原始数据。《免疫学前沿》（Frontiers in Immunology）。2025年；16卷：1620996。DOI：10.3389/fimmu.2025.1620996。 摘要 非典型溶血尿毒综合征（atypical hemolytic uremic syndrome, aHUS）是一种罕见且危重的血栓性微血管病，由遗传或获得性异常引发，导致细胞表面补体旁路途径激活。该过程会引发内皮功能障碍与微血管血栓形成。抗C5抗体的问世极大改善了非典型溶血尿毒综合征的预后，但此类治疗需定期静脉输注，且会阻断全身补体活性，使患者面临感染风险。近年来，研究人员开发出可选择性结合损伤相关靶分子的补体抑制剂，从而将药物富集于特定细胞或组织部位，同时保留全身补体功能。 本研究评估了利用C3d在细胞补体激活位点天然定位特性的新型分子的局部补体抑制活性，即与补体受体1（complement receptor 1, CR1）的前10或17个短共识重复序列（short consensus repeats, SCRs，分别记为CR11-10与CR11-17），或补体因子H（complement factor H, FH）的前5个SCRs（FH1-5）偶联的抗C3d单克隆抗体3d8b。为此，我们检测了它们在暴露于非典型溶血尿毒综合征患者血清的微血管内皮细胞（microvascular endothelial cells, HMEC-1）上阻断C3沉积与C5b-9复合物形成的能力。我们还评估了它们在预先暴露于非典型溶血尿毒综合征患者血清、随后用对照血液灌注的HMEC-1中，预防抗血栓特性丧失的能力。 结果显示，与CR11-10、CR11-17或FH1-5偶联的抗C3d抗体可有效阻断非典型溶血尿毒综合征患者血清诱导的HMEC-1补体激活，其效果优于非靶向可溶性同类制剂。C3转化酶抑制的效力因补体抑制组分不同而异（CR11-17 > CR11-10 > FH1-5）。但所有抑制剂均可成功阻断C5转化酶活性，并消除非典型溶血尿毒综合征患者血清的促血栓形成效应。本研究结果证实，组织靶向性补体抑制有望成为治疗非典型溶血尿毒综合征及其他以局部补体失调为特征的疾病的新型非全身性治疗策略。