scholarly journals Guillain-Barré syndrome following Zika virus infection is associated with a diverse spectrum of peripheral nerve reactive antibodies

Author(s):  
Alexander J Davies ◽  
Cinta Lleixà ◽  
Ana M Siles ◽  
Dawn Gourlay ◽  
Georgina Berridge ◽  
...  

Introduction 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 a consequence of autoimmunity or direct neurotoxicity is unclear. Methods We employed rat dorsal root ganglion (DRG) neurons, Schwann cells (SCs), and human stem cell-derived sensory neurons myelinated with rat SCs as cellular models to screen for anti-peripheral nerve reactive IgG and IgM autoantibodies in sera of ZIKV patients with and without GBS. In this study, 52 ZIKV-GBS patients were compared with 134 ZIKV-infected patients, 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 reactivity to rat SCs (6.5%) and myelinated co-cultures (9.6%) were significantly higher, albeit infrequently, in the ZIKV-GBS group compared to all controls. IgM antibody immunoreactivity to DRGs (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 anti-lipid antigen reaction characteristics. There was however no significant association of ZIKV-GBS with any anti-glycolipid antibodies. Conclusion Autoantibodies in ZIKV associated GBS patient sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

2021 ◽  
Author(s):  
Cinta Lleixà ◽  
Lorena Martín-Aguilar ◽  
Elba Pascual-Goñi ◽  
Teresa Franco ◽  
Marta Caballero ◽  
...  

Guillain-Barre Syndrome (GBS) is an acute inflammatory neuropathy with a heterogeneous presentation and pathogenesis. Serum antibodies against various gangliosides can be found in less than half of all patients in the acute phase of GBS but the target antigens remain unknown for the remaining half. Our work describes a comprehensive screening for serum autoantibodies targeting peripheral nerve tissue, cells, and purified antigens in a prospective GBS cohort including 100 patients. Our study confirms that (1) GBS patients display a very heterogeneous repertoire of autoantibodies targeting nerve cells and structures, (2) gangliosides are the most frequent antigens in GBS patients and have prognostic value, (3) a small subset of patients display antibodies targeting the myelin sheath, and (4) further antigen-discovery experiments are needed to elucidate other potential disease-specific autoantibodies in GBS.


2016 ◽  
Vol 375 (16) ◽  
pp. 1598-1601 ◽  
Author(s):  
Thais dos Santos ◽  
Angel Rodriguez ◽  
Maria Almiron ◽  
Antonio Sanhueza ◽  
Pilar Ramon ◽  
...  

PLoS Medicine ◽  
2017 ◽  
Vol 14 (1) ◽  
pp. e1002203 ◽  
Author(s):  
Fabienne Krauer ◽  
Maurane Riesen ◽  
Ludovic Reveiz ◽  
Olufemi T. Oladapo ◽  
Ruth Martínez-Vega ◽  
...  

2020 ◽  
Vol 27 (7) ◽  
Author(s):  
Kevan M Akrami ◽  
Betania Mara Freitas de Nogueira ◽  
Mateus Santana do Rosário ◽  
Laise de Moraes ◽  
Marli Tenório Cordeiro ◽  
...  

Zika virus cases in Brazil have diminished since emergence in 2015. We report Guillain Barré Syndrome caused by Zika and possible Chikungunya co-infection during an expected low arboviral season. This case highlights the importance of clinical vigilance for Zika in those with neurological syndromes outside typical arboviral season.


F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 196 ◽  
Author(s):  
Michel Jacques Counotte ◽  
Dianne Egli-Gany ◽  
Maurane Riesen ◽  
Million Abraha ◽  
Teegwendé Valérie Porgo ◽  
...  

Background. The Zika virus (ZIKV) outbreak in the Americas has caused international concern due to neurological sequelae linked to the infection, such as microcephaly and Guillain-Barré syndrome (GBS). The World Health Organization stated that there is “sufficient evidence to conclude that Zika virus is a cause of congenital abnormalities and is a trigger of GBS”. This conclusion was based on a systematic review of the evidence published until 30.05.2016. Since then, the body of evidence has grown substantially, leading to this update of that systematic review with new evidence published from 30.05.2016 – 18.01.2017, update 1. Methods. We review evidence on the causal link between ZIKV infection and adverse congenital outcomes and the causal link between ZIKV infection and GBS or immune-mediated thrombocytopaenia purpura. We also describe the transition of the review into a living systematic review, a review that is continually updated. Results. Between 30.05.2016 and 18.01.2017, we identified 2413 publications, of which 101 publications were included. The evidence added in this update confirms the conclusion of a causal association between ZIKV and adverse congenital outcomes. New findings expand the evidence base in the dimensions of biological plausibility, strength of association, animal experiments and specificity. For GBS, the body of evidence has grown during the search period for update 1, but only for dimensions that were already populated in the previous version. There is still a limited understanding of the biological pathways that potentially cause the occurrence of autoimmune disease following ZIKV infection. Conclusions. This systematic review confirms previous conclusions that ZIKV is a cause of congenital abnormalities, including microcephaly, and is a trigger of GBS. The transition to living systematic review techniques and methodology provides a proof of concept for the use of these methods to synthesise evidence about an emerging pathogen such as ZIKV.


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