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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.

Original publication

DOI

10.1212/nxi.0000000000200047

Type

Journal article

Journal

Neurology(R) neuroimmunology & neuroinflammation

Publication Date

01/2023

Volume

10

Addresses

From the Nuffield Department of Clinical Neurosciences (A.J.D., S.R.), University of Oxford, John Radcliffe Hospital, UK; Neuromuscular Diseases Unit (C.L., A.M.S., L.Q.), Neurology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Spain; Centro para la Investigación Biomédica en red en Enfermedades Raras-(CIBERER) Madrid (C.L., A.M.S., L.Q.), Spain; Institute of Infection (D.S.G., S.K.H., H.J.W.), Immunity & Inflammation, University of Glasgow, University Place, UK; Target Discovery Institute (G.B., R.F.), NDM Research Building, University of Oxford, Old Road Campus, UK; Wellcome Centre for Human Genetics (W.D., G.R.S., J.M.), Nuffield Department of Medicine, University of Oxford, UK; Center for Autoimmune Diseases Research (CREA) (C.R.-S., J.-M.A.), Universidad del Rosario, Bogotá, Colombia; Departamento de Medicina (A.K.F., C.M.R.-V.), Universidad del Norte, Barranquilla, Colombia; Grupo de Epidemiología y Salud Poblacional (GESP) (L.O.,), School of Public Health, Universidad del Valle, Cali, Colombia; Department of Microbiology (B.P.), School of Basic Sciences, Universidad del Valle, Cali, Colombia; Dengue Hemorrhagic Fever Research Unit (J.M.), Office for Research and Development, Siriraj Hospital, Faculty of Medicine, Mahidol Univeristy, Bangkok, Thailand; Department of Neurology (C.A.P.), Johns Hopkins University School of Medicine, Baltimore, MD; and LifeFactors (J.-M.A.), Rionegro, Colombia; Division of Emerging Infectious Disease (W.D.), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Keywords

Animals, Humans, Rats, Guillain-Barre Syndrome, Immunoglobulin G, Immunoglobulin M, Autoantibodies, Zika Virus, Zika Virus Infection