Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.
Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.
复制标题
DOI：
10.1212/nxi.0000000000200047
复制
发表时间：
2023-01
影响因子：
8.8
通讯作者：
Rinaldi, Simon
中科院分区：
文献类型：
--
作者：
Davies, Alexander J.;Lleixa, Cinta;Siles, Ana M.;Gourlay, Dawn S.;Berridge, Georgina;Dejnirattisai, Wanwisa;Ramirez-Santana, Carolina;Anaya, Juan-Manuel;Falconar, Andrew K.;Romero-Vivas, Claudia M.;Osorio, Lyda;Parra, Beatriz;Screaton, Gavin R.;Mongkolsapaya, Juthathip;Fischer, Roman;Pardo, Carlos A.;Halstead, Susan K.;Willison, Hugh J.;Querol, Luis;Rinaldi, Simon
最近在南美洲和中美洲爆发的寨卡病毒（ZIKV）凸显了显着的神经系统副作用。在1：4，000的ZIKV病例中观察到与炎性神经病Guillain-Barré综合征（GBS）的并发症。ZIKV感染的神经系统症状是否是免疫介导的尚不清楚。我们使用啮齿动物和人类活细胞模型来筛选患有ZIKV且伴有和不伴有GBS的患者的血清中的抗外周神经反应性IgG和IgM自身抗体。在这项研究中，将52名ZIKV-GBS患者与134名无GBS的ZIKV感染患者和91名非ZIKV对照进行了比较。阳性血清通过免疫沉淀和质谱法进行靶标鉴定，候选抗原通过ELISA和基于细胞的测定法进行验证。还在阵列上筛选针对糖脂抗原的自身抗体反应。总体而言，与所有对照组相比，ZIKV-GBS组中对大鼠雪旺细胞（SC）（6.5%）和有髓鞘共培养物（9.6%）的IgG抗体反应性显著更高，尽管不常见。与其他对照相比，在ZIKV-GBS组中更频繁地观察到对背根神经节神经元（32.3%）和SC（19.4%）的IgM抗体免疫反应性，而对共培养物的IgM反应性在ZIKV和非ZIKV血清中同样常见。确认来自1名患者的强轴突结合ZIKV-GBS血清IgG抗体与神经成束蛋白155和186反应。来自无GBS的ZIKV感染患者的血清显示出强髓鞘结合和推定的抗脂质抗原反应特征。然而，ZIKV-GBS与任何已知的抗糖脂抗体没有显著关联。ZIKV-GBS中的自身抗体应答靶向异质性外周神经抗原，表明尽管存在常见的前驱感染，但体液免疫应答具有异质性。
Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear. We used rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in the sera of patients with ZIKV with and without GBS. In this study, 52 patients with ZIKV-GBS were compared with 134 ZIKV-infected patients without GBS and 91 non-ZIKV controls. Positive sera were taken forward for target identification by immunoprecipitation and mass spectrometry, and candidate antigens were validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated cocultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared with all controls. IgM antibody immunoreactivity to dorsal root ganglia neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared with other controls, whereas IgM reactivity to cocultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from 1 patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV-infected patient without GBS displayed strong myelin-binding and putative antilipid antigen reaction characteristics. There was, however, no significant association of ZIKV-GBS with any known antiglycolipid antibodies. Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.