Antiganglioside antibodies--their pathophysiological effects on Guillain-Barré syndrome and variants

Gangliosides, N-acetylneuraminic acid (sialic acid)-bearing glycosphingolipids, are believed to reside in clusters within membrane microdomains, called lipid rafts or glycosynapse. Recent studies demonstrated that antiganglioside antibodies play an important role in the pathogenesis of Guillain-Barré syndrome (GBS) and Fisher syndrome (FS). The anti-GM1 antibodies are likely to damage peripheral nerves through complement activation with dysfunction of voltage-gated sodium channels. Some antiganglioside antibodies may cause dysfunction of voltage-gated calcium channels without complement activation. Clustered epitopes of ganglioside complexes (GSCs) consisting of two gangliosides can be targeted by serum antibodies in GBS and FS. Anti-GD1a/GD1b complex antibodies are associated with severe GBS. Approximately 50% of FS patients have antibodies to GSCs containing GQ1b or GT1a. Various glycolipids including GSCs may form complex glycolipid environment in the cell membrane, regulating the accessibility and the avidity of antiganglioside antibodies. In addition to antibody specificity, the glycolipid environment or specific distribution of target gangliosides in peripheral nervous system can influence pathogenic effects of antiganglioside antibodies in GBS and FS. Conformational and functional analyses of glycoepitopes of GSCs in the biological membrane will provide new vistas to research on antibody-antigen interaction in GBS, and shed light on microdomain function mediated by carbohydrate-to-carbohydrate interaction.     

Guillain-Barré syndrome in northwestern China.

We reviewed 100 patients with Guillan-Barré syndrome (GBS) from 1994 to 2000 from northwestern China. We examined clinical and electro-diagnostics features and compared them to patients from Europe, North America and northern China. Results indicated that among 100 patients with GBS, the demyelinating pattern was present in 51 patients, the axonal pattern in 25 patients, and 8 patients were inexcitable, 12 patients equivocal and 4 patients normal. The electrophysiological and clinical features of various subtypes of GBS in northwestern China seemed to be different in some ways from those in western countries and in northern China. However, in northwestern China, the demyelinating pattern is the major electrophysiological subtype.     

Complications of Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is an immune-mediated disorder in the peripheral nervous system with a wide spectrum of complications. A good understanding of the complications of GBS assists clinicians to recognize and manage the complications properly thereby reducing the mortality and morbidity of GBS patients. Herein, we systemically review the literature on complications of GBS, including short-term complications and long-term complications. We summarize the frequency, severity, clinical manifestations, managements and possible mechanisms of different kinds of complications, and point out the flaws of current studies as well as demonstrate the further investigations needed.     

Guillain-Barré syndrome in child with prolong intubation

Guillain-Barré syndrome (GBS) is an acute demyelinating disorder of the peripheral nervous system that results from an aberrant immune response directed at peripheral nerves. A typical GBS patient presents with rapidly ascending symmetrical weakness, which may progress to respiratory failure in 30% of patients. There are no definite criteria exists in GBS in children regarding prolonged ventilation. Here we report a child of GBS requiring prolonged intubation and ventilation for 60 days who afterward had a complete recovery. We present this case to highlight the importance that even in children prolonged intubation and ventilation of GBS case prognosis can be good.     

Pathogenicity of anti-ganglioside antibodies in the Guillain-Barré syndrome

Guillain-Barré syndrome (GBS) is a postinfectious inflammatory polyradiculo-neuropathy characterized by flaccid paralysis. Antibodies directed against glycolipid structures (gangliosides), which are highly expressed in the peripheral nervous system, are frequently detected in sera from GBS patients. These antibodies interfere with nerve conduction and have been shown to activate phagocytes via IgG receptors (FcgammaR). These findings support an important role of glycolipid-specific antibodies in the pathogenesis of GBS.     

Guillain-Barré syndrome following varicella-zoster virus infection

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4 weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4 weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40 years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1 year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.     

HLA-Antigens in Guillain-Barré Syndrome

A microlymphocytotoxicity test determined serologically the frequency of HLA antigens in 32 patients with Guillain-Barre syndrome and in 234 healthy control subjects. The results demonstrated significantly increased frequencies of A3 and B8. The relative risk was estimated to be 9.6 and 4.6 for the A3 and B8 antigens, respectively. Study of the gametic association revealed weak positive linkage disequilibrium and biological association. The results are discussed, and it is concluded that the aberrant genetic make-up of the patients makes them more susceptible to develop the syndrome after exposure to the environmental factor(s).     

Campylobacter jejuni enteritis and Guillain-Barré syndrome]

Some patients developed Guillain-Barré syndrome after the administration of bovine brain ganglioside. Patients with Guillain-Barré syndrome subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Miller Fisher syndrome, a variant of Guillain-Barré syndrome, is associated with IgG antibody to GQ1b ganglioside. My colleagues and I showed the existence of molecular mimicry between GM1 and lipopolysaccharide of C. jejuni isolated from a patient with Guillain-Barré syndrome, and that between GQ1b and C. jejuni lipopolysaccharides from patients with Miller Fisher syndrome. The glycotope mimicry between infectious agents and gangliosides may function in the production of antiganglioside antibodies and the development of Guillain-Barré syndrome and Miller Fisher syndrome.     

Guillain-Barré syndrome and cytomegalovirus infection during pregnancy

Guillain-Barré syndrome (GBS) is an immune-mediated disorder which can be triggered by cytomegalovirus (CMV) infection. GBS following CMV primary infection is a rare event during pregnancy, which raises the question of maternal and fetal management. We describe an unusual case of GBS after CMV primary infection in a pregnant woman. The mother was successfully treated with standard immunoglobulins but in utero fetal death caused by CMV congenital infection unfortunately occurred. Similar cases have rarely been reported in the literature.     

Case report: Hepatitis A preceding Guillain-Barré syndrome

A case of acute hepatitis A with Guillain-Barré Syndrome subtype AMAN (acute motor axonal neuropathy) in a 17-year-old male is reported. Serum and cerebrospinal fluid were positive for anti-hepatitis A virus (HAV) IgM, IgG, and IgA. The onset of the syndrome was evident in week 3 of illness. The remarkably high titers of serum anti-HAV IgG appeared unique to a hepatitis A patient with the syndrome. Phylogenetic analysis of the HAV genome detected in the serum and feces revealed genotype IIIA, circulating commonly in Pune, western India.     

Response of Toll-like receptors in experimental Guillain-Barré syndrome: a kinetic analysis

Guillain-Barré syndrome (GBS) is an autoimmune disorder caused by the interaction between cellular and humoral immune responses in the peripheral nervous system. Toll-like receptors (TLRs) are key players in innate and have regulatory functions in adaptive immunity. In this study, we systematically examined expression patterns of TLRs in sciatic nerve and lymphoid organs during the disease course of murine experimental autoimmune neuritis and in blood from Guillain-Barré patients. A kinetic response pattern was identified, characterized by a pronounced up-regulation of TLR2, 6 and 11 on T cells and TLR4 and 6 on APCs, while TLR1 expression was decreased. Moreover, an enhanced expression of the disease promoting cytokine Interleukin-(IL)17A was detected. Additional analysis of GBS patients revealed an up-regulation of TLR2, TLR4 and TLR6 mRNA, negatively correlated with disease severity. This first systematic analysis of TLR expression pattern may contribute to elucidating the role of TLRs in GBS pathophysiology.     

Guillain-Barré syndrome in association with COVID-19 vaccination: a systematic review

Since the beginning of worldwide vaccination against coronavirus disease 2019 (COVID-19), studies have reported a possible association between vaccination and Guillain-Barré syndrome (GBS). In this regard, we conducted a systematic review assessing different demographic, clinical, and neurophysiological aspects of patients with GBS following immunization with COVID-19 vaccines. A comprehensive search of PubMed, Web of Science, Scopus, and Google Scholar was performed. Articles in English between January 2020 and November 2021 were included. Data on demographics, clinical characteristics, vaccines information, treatment approaches, and outcomes were extracted. The data of a total of 88 patients out of 41 studies was included. The mean age of patients was 58.7?±?16.6 years and 55 cases (62.5%) were male. AstraZeneca was the most-reported vaccine associated with GBS with 52 cases (59.1%) followed by Pfizer with 20 cases (22.7%). GBS occurred after the first dose of vaccination in 70 cases (79.5%). The mean time interval between vaccination and symptom onset was 13.9?±?7.4 days. Limb weakness (47.7%), sensory disturbance (38.6%), and facial weakness (27.3%) were the most common reported symptoms, respectively. Albuminocytologic dissociation was seen in 65% of patients who underwent lumbar puncture (n?=?65). Acute inflammatory demyelinating polyradiculopathy was the most common GBS subtype, which was reported in 38 patients (43.2%). While one-fifth of patients underwent intubation (n?=?17), a favorable outcome was achieved in the majority of subjects (n?=?46, 63%). Overall, a small rise in GBS incidence, following various COVID-19 vaccines, was observed. Notably, 85% of affected individuals experienced at least a partial recovery.

     

Elevated number of cells secreting transforming growth factor beta in Guillain-Barré syndrome

We used ELISPOT and cell ELISA to study secretion of IL-4, IFN-gamma, TGF-beta, IL-6, and TNF-alpha by circulating mononuclear cells during the course of Guillain-Barré syndrome (GBS). Compared to healthy controls, patients with GBS had higher numbers of TGF-beta-secreting cells and the number of individuals with myelin-peptide-induced IL-4 and TGF-beta secretion was higher in the GBS group. No significant differences were seen concerning the predominantly pro-inflammatory cytokines IFN-gamma, IL-6 or TNF-alpha. Our findings indicate a down-regulatory role for TGF-beta and IL-4 in GBS.