Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies
Davies, Alexander J.
Lleixà, Cinta (Institut d'Investigació Biomèdica Sant Pau)
Siles, Ana Maria (Institut d'Investigació Biomèdica Sant Pau)
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 (Institut d'Investigació Biomèdica Sant Pau)
Rinaldi, Simon
Universitat Autònoma de Barcelona

Data:	2022
Resum:	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.
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Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Publicat a:	Neurology® neuroimmunology & neuroinflammation, Vol. 10 (november 2022) , ISSN 2332-7812

DOI: 10.1212/NXI.0000000000200047
PMID: 36411078

14 p, 917.7 KB

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