Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies
DAVIES AJ., Lleixà C., Siles AM., Gourlay D., BERRIDGE G., DEJNIRATTISAI W., Ramírez-Santana C., Anaya J-M., Falconar AK., Romero-Vivas CM., Osorio L., Parra B., SCREATON GR., MONGKOLSAPAYA J., FISCHER R., Pardo CA., Halstead SK., Willison HJ., Querol L., RINALDI S.
Background and Objectives Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurological side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4000 ZIKV cases. Whether the neurological symptoms of ZIKV infection are immune-mediated is unclear. We employed rodent and human live cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in sera of ZIKV patients with and without GBS. Methods In this study, 52 ZIKV-GBS patients 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 validated by ELISA and cell-based assays. Autoantibody reactions against glycolipid antigens were also screened on an array. Results Overall, IgG antibody reactivities to rat Schwann cells (SCs) (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequent, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to dorsal root ganglia (DRG) neurones (32.3%) and SCs (19.4%) was more frequently observed in the ZIKV-GBS group compared to other controls, while IgM reactivity to co-cultures was as common in ZIKV and non-ZIKV sera. Strong axonal-binding ZIKV-GBS serum IgG antibodies from one patient were confirmed to react with neurofascin 155 and 186. Serum from a ZIKV non-GBS patient displayed strong myelin-binding and putative anti-lipid antigen reaction characteristics. There was however no significant association of ZIKV-GBS with any known anti-glycolipid antibodies. Conclusion Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.