Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies

• Published in: Neurology : neuroimmunology & neuroinflammation Vol. 10; no. 1
• Main Authors: Davies, Alexander J., Lleixà, Cinta, Siles, Ana M., Gourlay, Dawn S., Berridge, Georgina, Dejnirattisai, Wanwisa, Ramírez-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
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 21.11.2022
• ISSN: 2332-7812
• DOI: 10.1212/NXI.0000000000200047

Background and ObjectivesRecent 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.MethodsIn 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.ResultsOverall, 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.DiscussionAutoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.