Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome
Immunological features and functional analysis of anti-CFH autoantibodies in patients with atypical hemolytic uremic syndrome
复制标题
非典型溶血性尿毒综合征患者抗CFH自身抗体的免疫学特征及功能分析
DOI：
10.1007/s00467-018-4074-4
复制
发表时间：
2019-02-01
影响因子：
3
通讯作者：
Zhao, Ming-hui
中科院分区：
文献类型：
--
作者：
Guo, Wei-yi;Song, Di;Zhao, Ming-hui
目的非典型溶血性尿毒症综合征（aHUS）与补体调节缺陷有关。抗补体因子 H (CFH) 抗体被认为参与 aHUS 的发病机制。本研究的目的是探讨中国汉族 aHUS 患者中 CFH 自身抗体的功能和特性。方法本研究涉及 36 名处于疾病急性期的抗 CFH 抗体阳性 aHUS 患者。收集患者的临床数据。通过 ELISA 检测抗 CFH 免疫球蛋白 G (IgG) 亚类和抗体同种型。使用重组 CFH 片段（SCR 1-4、SCR 7、SCR 11-14 和 SCR 19-20）进行表位作图。使用从 7 名患者血浆中纯化的 IgG 进行功能分析。结果所有患者均出现 HUS 的经典三联征。抗 CFH 自身抗体主要与 CFH 的 SCR 19-20 结构域结合，但不与 SCR 1-4 结构域结合。在七名患者中，CFI 辅因子活性均未受到抗 CFH 抗体的干扰。在所有 7 名患者中，纯化的 IgG 干扰了 CFH 与 C3b 的结合以及 CFH 介导的绵羊红细胞保护。来自 4/5 (80%) 测试患者的 IgG 抑制了 CFH 与肾小球内皮细胞的结合。结论我们的研究表明，aHUS 患者的 CFH 抗体的特性，包括对 SCR 和 IgG 亚类的识别，可以影响和损害 CFH 的生物学作用，从而导致 aHUS 易感性。
ObjectiveAtypical hemolytic uremic syndrome (aHUS) is associated with defective complement regulation. Anti-complement factor H (CFH) antibodies were thought to participate in the pathogenesis of aHUS. The aim of this study was to address the functions and properties of CFH autoantibodies in a Chinese Han cohort of aHUS patients.MethodsThirty-six anti-CFH antibody-positive aHUS patients at the acute phase of the disease were involved in this study. Clinical data of the patients were collected. Anti-CFH immunoglobulin G (IgG) subclasses and antibody isotypes were detected by ELISA. Epitope mapping was performed using recombinant CFH fragments (SCRs 1–4, SCR 7, SCRs 11–14, and SCRs 19–20). Purified IgG from plasma from seven patients were used for functional analyses.ResultsAll patients presented with the classic triad of HUS. The anti-CFH autoantibodies mostly bound to the SCRs 19–20 domains of CFH but not the SCRs 1–4 domains. CFI cofactor activity was not disturbed by the anti-CFH antibody in any of the seven patients. Purified IgG interfered with the binding of CFH to C3b and CFH-mediated sheep erythrocyte protection in all seven patients. IgG from 4/5 (80%) patients tested inhibited the binding of CFH to glomerular endothelial cells.ConclusionsOur study suggests that the properties of CFH antibodies from patients with aHUS, including the recognition of SCRs and IgG subclasses, can influence and impair the biological role of CFH and therefore contribute to aHUS susceptibility.