Guillain–Barré Syndrome Associated with JEV Infection

Wang, Guowei; Li, Haining; Yang, Xiaobo; Guo, Tao; Wang, Libin; Zhao, Zhen; Sun, Haifeng; Hou, Xiaolin; Ding, Xiangchun; Dou, Chunyang; Ma, Qiaoli; Yang, Xiao; Wang, Yanbo; Wang, Zhao; Wang, Luxuan; Liu, Jixiang; Wang, Zhenhai; Wang, Huanyu; Xie, Peng

doi:10.1056/nejmc1916977

Cited by 31 publications

(41 citation statements)

References 4 publications

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“…Pathologically, it has been suggested that impairment of the BBB is conclusively correlated with neuroinflammation. During JEV infection, dramatic BBB damage occurs, which is associated with Guillain-Barre syndrome ( Wang et al., 2020 ). Currently, there are no effective therapeutics against JE ( Misra and Kalita, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Zou

Xiong

et al. 2021

Front. Cell. Infect. Microbiol.

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Infection with Japanese encephalitis virus (JEV) induces high morbidity and mortality, including potentially permanent neurological sequelae. However, the mechanisms by which viruses cross the blood-brain barrier (BBB) and invade into the central nervous system (CNS) remain unclear. Here, we show that extracellular HMGB1 facilitates immune cell transmigration. Furthermore, the migration of immune cells into the CNS dramatically increases during JEV infection which may enhance viral clearance, but paradoxically expedite the onset of Japanese encephalitis (JE). In this study, brain microvascular endothelial cells (BMECs) were utilized for the detection of HMGB1 release, and leucocyte, adhesion, and the integrity of the BBB in vitro. Genetically modified JEV-expressing EGFP (EGFP-JEV) and the BBB model were established to trace JEV-infected immune cell transmigration, which mimics the process of viral neuroinfection. We find that JEV causes HMGB1 release from BMECs while increasing adhesion molecules. Recombinant HMGB1 enhances leukocyte-endothelium adhesion, facilitating JEV-infected monocyte transmigration across endothelia. Thus, JEV successfully utilizes infected monocytes to spread into the brain, expanding inside of the brain, and leading to the acceleration of JE onset, which was facilitated by HMGB1. HMGB1-promoted monocyte transmigration may represent the mechanism of JEV neuroinvasion, revealing potential therapeutic targets.

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Section: Introductionmentioning

confidence: 99%

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Zou

Xiong

et al. 2021

Front. Cell. Infect. Microbiol.

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“…On the contrary, 9% of patients (4/47) manifested demyelination and 85% of patients (40/47) manifested axonal degeneration in the nerve conduction study from a Chinese case series. 40 Intriguingly we found that patients who are positive for anti-chikungunya immunoreactivity exhibited a significantly shorter duration of neurologic symptoms.…”

Section: Discussionmentioning

confidence: 71%

Antecedent infections inGuillain‐Barrésyndrome patients from south India

Dutta

Debnath

Nagappa

et al. 2021

J Peripheral Nervous Sys

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Guillain-Barré syndrome (GBS) is the commonest post-infectious inflammatory peripheral neuropathy with undiscerned aetiology. The commonly reported antecedent infections implicated in India include Campylobacter jejuni, chikungunya, dengue, and Japanese encephalitis (JE). In this study from south India, we investigated the role of these four agents in triggering GBS. This case-control study was performed on 150 treatment-naive patients with GBS and 150 age and sex-matched controls from the same community. IgM immunoreactivity for C. jejuni, chikungunya, and dengue was detected by enzyme-linked immunosorbent assay (ELISA) in serum of patients with GBS and control subjects. Immunoreactivity against JE was detected in serum as well as cerebrospinal fluid (CSF) from patients (n = 150) and orthopaedic control (n = 45) subjects. The immunoreactivity against infections was compared between demyelinating and axonal subtypes of GBS. Overall, 119/150 patients with GBS had serological evidence of antecedent infection. Amongst those with evidence of antecedent infection, 24 (16%), 8 (5%), and 9 (6%) patients were exclusively immunoreactive to chikungunya, JE, and C. jejuni, respectively. In the remaining patients (78/119), immunoreactivity to multiple pathogens was noted. Immunoreactivity to C. jejuni infection was found in 32% of GBS patients compared to 2.7% controls (P < .001), whereas to chikungunya virus was reported in 66.7% of patients with GBS compared to 44.7% controls (P = .006). Anti-dengue immunoreactivity was significantly associated with the demyelinating subtype of GBS. Patients positive for JE IgM (CSF) manifested demyelinating electrophysiology. In this large case-control study, immunoreactivity against multiple infectious agents was observed in a subset of patients.Chikungunya was the commonest antecedent infection, followed by C. jejuni.

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“…Third, the continued development of the infection may cause a severe humoral immune response in the central and peripheral nervous systems, which further exacerbates clinical symptoms and cognitive impairment. Previous studies have reported increases in immunoglobulins M and G in the cerebrospinal fluid, as well as circulating B lymphocytes and plasma cells (6,18,19). Therefore, optimal treatment requires consideration of all three pathogenic mechanisms of JE, and should comprise not only an early anti-viral effect, but also counteractive measures for the subsequent inflammatory reaction, cytokine storm, and humoral immune response.…”

Section: Discussionmentioning

confidence: 99%

“…The second component is the production of antibodies against the patient's nerve tissue. A prior study ( 19 ) reported that 30% of patients with JEV infection develop antibodies to their gangliosides (GM1, GM2, GD1a, and GD1b), resulting in Guillain-barre syndrome. Thus, the continued progression of JEV into the later stages may result in the generation of auto-antibodies, which damage peripheral nerves and increase the risk of disability.…”

Section: Discussionmentioning

confidence: 99%

“…The ability of IVIG to neutralise antibodies in JEV-positive patients has been previously demonstrated in a randomised double-blind placebo-controlled trial ( 35 ). Another study ( 19 ) reported that the administration of IVIG within 2 weeks of symptom onset could effectively treat Guillain-barre syndrome associated with JEV; after 1 week of treatment, 54% of patients experienced significant improvements in clinical signs and symptoms. In our study, we administered a high dose for 5 days, and continued to provide IVIG at 5–10 g/d for 1 week; this may have led to the complete neutralisation of the autoantibodies and a large reduction in damage to the central nervous system.…”

Section: Discussionmentioning

confidence: 99%

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The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis

et al. 2021

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Objective: There is currently no effective treatment for Japanese encephalitis, which has a high rate of morbidity and mortality. This study assessed the effectiveness of a ganciclovir, methylprednisolone, and immunoglobulin combination (TAGMIC) therapy in decreasing cognitive impairment and mortality among patients with Japanese encephalitis.Methods: We retrospectively assessed the clinical data of 31 patients diagnosed with Japanese encephalitis, who were admitted to an intensive care unit. Patients were divided into the TAGMIC and non-TAGMIC group according to their treatment regime. We compared the 60-day, 6-month, and overall mortality and survival curves between groups. We also compared Barthel Index scores, Montreal Cognitive Assessment (MoCA) scores, and diffusion tensor imaging (DTI) results.Results: There was no significant difference in the 30-day mortality rate or Kaplan–Meier survival curve between groups. The 60-day, 6-month, and overall mortality rates in the TAGMIC group were significantly reduced (P = 0.043, P = 0.018, and P = 0.018, respectively) compared with the non-TAGMIC group (0, 0, 0 vs. 31.25, 37.5, 37.5%, respectively). The 60-day, 6-month, and overall Kaplan–Meier survival curves were significantly different between groups (P = 0.020, P = 0.009, P = 0.009, respectively). There was no significant difference in the Barthel Index scores of surviving patients. Among the five patients who underwent MoCA and DTI, four had a score of 0/5 for delayed recall (no cue), while the remaining patient had a score of 2/5. All five patients were able to achieve a score of 5/5 with classification and multiple-choice prompts, and had sparse or broken corpus callosum (or other) fibre bundles.Conclusion: TAGMIC treatment can reduce mortality due to severe Japanese encephalitis. The memory loss of surviving patients is mainly due to a disorder of the memory retrieval process, which may be related to the breakage of related fibre bundles.

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Guillain–Barré Syndrome Associated with JEV Infection

Cited by 31 publications

References 4 publications

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Brain Microvascular Endothelial Cell-Derived HMGB1 Facilitates Monocyte Adhesion and Transmigration to Promote JEV Neuroinvasion

Antecedent infections inGuillain‐Barrésyndrome patients from south India

The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis

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