PT - JOURNAL ARTICLE AU - Davies, Alexander J. AU - Lleixà, Cinta AU - Siles, Ana M. AU - Gourlay, Dawn S. AU - Berridge, Georgina AU - Dejnirattisai, Wanwisa AU - Ramírez-Santana, Carolina AU - Anaya, Juan-Manuel AU - Falconar, Andrew K. AU - Romero-Vivas, Claudia M. AU - Osorio, Lyda AU - Parra, Beatriz AU - Screaton, Gavin R. AU - Mongkolsapaya, Juthathip AU - Fischer, Roman AU - Pardo, Carlos A. AU - Halstead, Susan K. AU - Willison, Hugh J. AU - Querol, Luis AU - Rinaldi, Simon TI - Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies AID - 10.1212/NXI.0000000000200047 DP - 2023 Jan 01 TA - Neurology - Neuroimmunology Neuroinflammation PG - e200047 VI - 10 IP - 1 4099 - http://nn.neurology.org/content/10/1/e200047.short 4100 - http://nn.neurology.org/content/10/1/e200047.full SO - Neurol Neuroimmunol Neuroinflamm2023 Jan 01; 10 AB - Background and Objectives 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.Methods 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.Results 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.Discussion Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.ALCAM=activated leukocyte cell adhesion molecule; ANOVA=analysis of variance; ANXA2=annexin A2; AMAN=acute motor axonal form of GBS; AXL=Axl receptor tyrosine kinase; CNTN1=contactin 1; DENV=dengue virus; DPYSL2=dihydropyrimidinase-related protein 2; DRG=dorsal root ganglia; Fc=fragment crystalizable region (of antibody); GBS=Guillain-Barré syndrome; GFRA1=glial cell-derived neurotrophic factor family receptor alpha-1; hiPSC=human induced pluripotent stem cell; HRP=horse radish peroxidase; IgG=immunoglobulin G; IgM=immunoglobulin M; ITGA7=integrin alpha 7; L1CAM=neural cell adhesion molecule L1; MS/MS=tandem mass spectrometry; MOPS=3-(N-morpholino)propanesulfonic acid; NCAM1=neural cell adhesion molecule 1; NEP=neprilysin; NF155=neurofascin 155 isoform; NF186=neurofascin 186 isoform; NF200=neurofilament heavy chain (200 kDa); NFASC=neurofascin; NHS=normal human serum; NKCC1=solute carrier Na-K-2Cl cotransporter 1; NrCAM=neuronal cell adhesion molecule; PRX=periaxin; SC=Schwann cell; SEM=standard error of the mean; TGFBR3=transforming growth factor receptor type 3; VINC=vinculin; ZIKV=Zika virus; ZIKV-CON=ZIKV-infected patients without neurologic complications; ZIKV-OND=ZIKV infection and other inflammatory neurologic diseases