Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Leonhard, Sonja E.; Halstead, Susan K.; Lant, Suzannah; Albuquerque, Maria de Fátima Pessoa Militão de; Brito, Carlos; Albuquerque, Livia Brito Bezerra de; Ellul, Mark; França, Rafael Freitas de Oliveira; Gourlay, Dawn; Griffiths, Michael J.; Henriques-Souza, Adélia Maria de Miranda; Machado, Maria Íris de Morais; Medialdea-Carrera, Raquel; Mehta, Ritvik P.; Melo, Roberta da Paz; Mesquita, Solange Dornelas; Moreira, Álvaro José Porto; Pena, Lindomar; Santos, Marcela Lopes; Turtle, Lance; Solomon, Tom; Willison, Hugh J.; Jacobs, Bart C.; Ferreira, Maria Lúcia Brito

doi:10.1016/j.jns.2020.117272

Cited by 26 publications

(31 citation statements)

References 47 publications

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“…An increased occurrence of AIDP after the Zika virus infection has also been demonstrated [20]. Although an association between a specific anti-ganglioside antibody and Zika virus-related GBS has not been demonstrated [21], peptide sharing was suggested among proteins of the Zika virus, cytomegalovirus, and the human peripheral nervous system [22,23]. Recently, a conflicting discussion on the association between SARS-CoV2 infection (i.e., and AIDP has become a topic of research [24][25][26].…”

Section: Gbsmentioning

confidence: 99%

Macrophages and Autoantibodies in Demyelinating Diseases

Koike

Katsuno

2021

Cells

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Myelin phagocytosis by macrophages has been an essential feature of demyelinating diseases in the central and peripheral nervous systems, including Guillain–Barré syndrome (GBS), chronic inflammatory demyelinating polyneuropathy (CIDP), and multiple sclerosis (MS). The discovery of autoantibodies, including anti-ganglioside GM1 antibodies in the axonal form of GBS, anti-neurofascin 155 and anti-contactin 1 antibodies in typical and distal forms of CIDP, and anti-aquaporin 4 antibodies in neuromyelitis optica, contributed to the understanding of the disease process in a subpopulation of patients conventionally diagnosed with demyelinating diseases. However, patients with these antibodies are now considered to have independent disease entities, including acute motor axonal neuropathy, nodopathy or paranodopathy, and neuromyelitis optica spectrum disorder, because primary lesions in these diseases are distinct from those in conventional demyelinating diseases. Therefore, the mechanisms underlying demyelination caused by macrophages remain unclear. Electron microscopy studies revealed that macrophages destroy myelin as if they are the principal players in the demyelination process. Recent studies suggest that macrophages seem to select specific sites of myelinated fibers, including the nodes of Ranvier, paranodes, and internodes, for the initiation of demyelination in individual cases, indicating that specific components localized to these sites play an important role in the behavior of macrophages that initiate myelin phagocytosis. Along with the search for autoantibodies, the ultrastructural characterization of myelin phagocytosis by macrophages is a crucial step in understanding the pathophysiology of demyelinating diseases and for the future development of targeted therapies.

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Section: Gbsmentioning

confidence: 99%

Macrophages and Autoantibodies in Demyelinating Diseases

Koike

Katsuno

2021

Cells

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“…However, we did not find a significant statistical association of ZIKV-GBS patient cases with any anti-glycolipid antibody signature, thereby supporting the results from a recent cohort study from Northeast Brazil. [25] The cases we did find may represent a subset of ZIKV induced GBS, or merely have been cases of classical onset GBS patients whose clinical course coincided with recent ZIKV infections.…”

Section: Discussionmentioning

confidence: 77%

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

Davies

Lleixà

Siles

et al. 2021

Preprint

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IntroductionRecent 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.MethodsWe 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 IgG and IgM autoantibodies reactive to peripheral nerve 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.ResultsOverall, 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 no significant association of ZIKV-GBS with any anti-glycolipid antibodies.ConclusionAutoantibodies in ZIKV associated GBS patients’ sera target heterogeneous peripheral nerve antigens suggesting heterogeneity of the humoral immune response despite a common prodromal infection.

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“…However, severe neurological manifestations and an increased number of GBS cases were reported in the 2013 French Polynesia outbreak [ 106 , 107 ]. In fact, following the spread of ZIKV, countries and territories, including Brazil, have reported an increased incidence of GBS cases following recent ZIKV infection [ 108 , 109 , 110 , 111 ]. It has been shown that GBS is slightly more common in men than in women, and limb weakness and areflexia/hyporeflexia are the most frequent clinical findings [ 112 ].…”

Section: Viruses Commonly Associated With Cns Infection In Brazilmentioning

confidence: 99%

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

Sousa

Santos

Paula

et al. 2021

Viruses

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Virus-induced infections of the central nervous system (CNS) are among the most serious problems in public health and can be associated with high rates of morbidity and mortality, mainly in low- and middle-income countries, where these manifestations have been neglected. Typically, herpes simplex virus 1 and 2, varicella-zoster, and enterovirus are responsible for a high number of cases in immunocompetent hosts, whereas other herpesviruses (for example, cytomegalovirus) are the most common in immunocompromised individuals. Arboviruses have also been associated with outbreaks with a high burden of neurological disorders, such as the Zika virus epidemic in Brazil. There is a current lack of understanding in Brazil about the most common viruses involved in CNS infections. In this review, we briefly summarize the most recent studies and findings associated with the CNS, in addition to epidemiological data that provide extensive information on the circulation and diversity of the most common neuro-invasive viruses in Brazil. We also highlight important aspects of the prion-associated diseases. This review provides readers with better knowledge of virus-associated CNS infections. A deeper understanding of these infections will support the improvement of the current surveillance strategies to allow the timely monitoring of the emergence/re-emergence of neurotropic viruses.

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Guillain-Barré syndrome during the Zika virus outbreak in Northeast Brazil: An observational cohort study

Cited by 26 publications

References 47 publications

Macrophages and Autoantibodies in Demyelinating Diseases

Macrophages and Autoantibodies in Demyelinating Diseases

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

Viral and Prion Infections Associated with Central Nervous System Syndromes in Brazil

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