The Association of Anti-Ganglioside Antibodies in the Pathogenesis and Development of Zika-Associated Guillain-Barré Syndrome

Abstract

Zika virus (ZIKV) has created major outbreaks all over the Americas and has caused severe neurological complications. The main neurological complications linked to ZIKV are Guillain-Barré syndrome (GBS), encephalitis, myelitis, and microcephaly. We thoroughly searched for published literature on PubMed and found evidence supporting the relationship between ZIKV and GBS. Through April 1, 2020, 429 publications were available on PubMed using the words "Zika associated GBS." Among these, only four results linked anti-ganglioside antibodies to Zika-associated GBS. So, we expanded our search to other platforms like PubMed Central® (PMC), Google Scholar, and Cochrane, after which we shortlisted 28 studies. These studies include review articles, observational studies, case series, and case reports. The information collected from these articles were mainly based on the outbreaks in Latin America and the results that these patients showed in the course of the disease. It took a lag time of 7-10 days for the patients to develop Zika-associated GBS. We used all the evidence regarding the epidemiology, clinical manifestations, neurological complications, and diagnostic criteria that supported the findings of anti-ganglioside antibodies to ZIKV-associated GBS. Patients were detected with the presence of these antibodies in their urine through the enzyme-linked immunosorbent assay (ELISA) test. But the mechanism by which the ZIKV causes other complications like myelitis and encephalitis is still unknown and yet to be explored to develop treatment and management strategies.

Nerve Ultrasound as Helpful Tool in Polyneuropathies

“…The acute variant of an immune-mediated neuropathy, GBS, is mostly preceded by an infectious gastrointestinal or pulmonary disease, most frequently by Campylobacter jejuni infection. Other associations with Zika, Cytomegaly and severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection have been described [ 109 , 110 , 111 ]. Clinical symptoms are distally arising sensory and predominantly motor symptoms leading to tetraparesis including autonomic dysregulation and cranial nerve palsies.…”

Peripheral nervous system is injured by neutrophil extracellular traps (NETs) elicited by nonstructural (NS) protein‐1 from Zika virus

“…Epidemiological data confirm that this disorder is the most common and most acute severe paralytic neuropathy, affecting approximately 100 000 people worldwide each year, and several reports show an increase in GBS cases concomitant with ZIKV epidemics 7,8 . Molecular mimicry is one of the potential mechanisms of ZIKV‐associated GBS, although this hypothesis lacks enough supporting evidence 9 . Infection of ZIKV in Schwann cells (SC), the principal glial cells of the peripheral nervous system (PNS), and in human myoblasts has also been associated with GBS 10–12 .…”

“…7,8 Molecular mimicry is one of the potential mechanisms of ZIKV-associated GBS, although this hypothesis lacks enough supporting evidence. 9 Infection of ZIKV in Schwann cells (SC), the principal glial cells of the peripheral nervous system (PNS), and in human myoblasts has also been associated with GBS. [10][11][12] Thus, the ZIKV-associated neuroinflammation needs to be better investigated.…”

Bioinformatic analyses hinted at augmented T helper 17 cell differentiation and cytokine response as the central mechanism of COVID‐19–associated Guillain‐Barré syndrome

“…11,12 Depending on the type of peripheral nerve involved, patients of GBS could present with paraesthesia or pain, acute symmetric ascending motor weakness (the most severe manifestation is respiratory failure due to respiratory muscle weakness) or autonomic abnormalities (eg orthostatic hypotension, disturbances of heart rate and rhythm). 13,14 Infections with Campylobacter jejuni and cytomegalovirus are two major risk factors of GBS. 15,16 In C jejuni-associated GBS cases, molecular mimicry between the ganglioside-like structures in lipo-oligosaccharides of the bacterium and gangliosides on the axonal surface contributes to the cross-reactivity of autoantibodies.…”

“…In contrast, B cell–mediated humoral immunity is strongly associated with AMAN and Miller Fisher syndrome, in which autoantibodies are produced to bind to gangliosides GM1 and GD1a at the nodes of Ranvier and/or anti‐GQ1b in the paranodal region 11,12 . Depending on the type of peripheral nerve involved, patients of GBS could present with paraesthesia or pain, acute symmetric ascending motor weakness (the most severe manifestation is respiratory failure due to respiratory muscle weakness) or autonomic abnormalities (eg orthostatic hypotension, disturbances of heart rate and rhythm) 13,14 . Infections with Campylobacter jejuni and cytomegalovirus are two major risk factors of GBS 15,16 .…”