Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies
<strong>Background and Objectives<br></strong> 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 c...
| المؤلفون الرئيسيون: | , , , , , , , , , , , , , , , , , , , |
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| التنسيق: | Journal article |
| اللغة: | English |
| منشور في: |
Lippincott, Williams & Wilkins
2022
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| _version_ | 1826309391520890880 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Davies, AJ |
| collection | OXFORD |
| description | <strong>Background and Objectives<br></strong>
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.
<br><strong>
Methods<br></strong>
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.
<br><strong>
Results<br></strong>
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.
<br><strong>
Conclusion<br></strong>
Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection. |
| first_indexed | 2024-03-07T07:33:28Z |
| format | Journal article |
| id | oxford-uuid:7de35009-d00d-47ee-b443-af7e3798a34d |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:33:28Z |
| publishDate | 2022 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:7de35009-d00d-47ee-b443-af7e3798a34d2023-02-21T11:26:51ZGuillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7de35009-d00d-47ee-b443-af7e3798a34dEnglishSymplectic ElementsLippincott, Williams & Wilkins2022Davies, AJLleixà, CSiles, AMGourlay, DBerridge, GDejnirattisai, WRamírez-Santana, CAnaya, J-MFalconar, AKRomero-Vivas, CMOsorio, LParra, BScreaton, GRMongkolsapaya, JFischer, RPardo, CAHalstead, SKWillison, HJQuerol, LRinaldi, S<strong>Background and Objectives<br></strong> 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. <br><strong> Methods<br></strong> 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. <br><strong> Results<br></strong> 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. <br><strong> Conclusion<br></strong> Autoantibody responses in ZIKV-GBS target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection. |
| spellingShingle | 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 Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title | Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title_full | Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title_fullStr | Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title_full_unstemmed | Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title_short | Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
| title_sort | guillain barre syndrome following zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies |
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