Large-scale profiling of antibody reactivity to glycolipids in patients with Guillain-Barré syndrome.

Guillain-Barré syndrome is an acute polyradiculoneuropathy in which preceding infections often elicit the production of antibodies that target peripheral nerve antigens, principally gangliosides. Anti-ganglioside antibodies are thought to play a key role in the clinical diversity of the disease and can be helpful in clinical practice. Extensive research into clinical associations of individual anti-ganglioside antibody specificities has been performed.

Guillain-Barré syndrome after the Zika epidemic in Colombia: A multicenter, matched case-control study.

Background: Zika produced the highest increase in the incidence of Guillain-Barré syndrome (GBS) in Latin America in the last decade. The Neuroinfections Emerging in the Americas Study (NEAS) was established in 2016 to investigate the association of emerging infectious disorders with GBS in Colombia. The present study assessed the role of preceding infections, including arboviruses and other pathogens, as risk factors for GBS.

Inter-Laboratory Validation of Nodal/Paranodal Antibody Testing.

Background And Aims: Reliable detection of antibodies against nodal targets is vital for the diagnosis of autoimmune nodopathies. The performance characteristics of recently developed in-house assays are unknown. We compared testing at four centres.

Swab pooling enables rapid expansion of high-throughput capacity for SARS-CoV-2 community testing.

Background: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement.

Objective: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline.

Serum anti-GM2 and anti-GalNAc-GD1a ganglioside IgG antibodies are biomarkers for immune-mediated polyneuropathies in cats.

Recent work identified anti-GM2 and anti-GalNAc-GD1a IgG ganglioside antibodies as biomarkers in dogs clinically diagnosed with acute canine polyradiculoneuritis, in turn considered a canine equivalent of Guillain-Barré syndrome. This study aims to investigate the serum prevalence of similar antibodies in cats clinically diagnosed with immune-mediated polyneuropathies. The sera from 41 cats clinically diagnosed with immune-mediated polyneuropathies (IPN), 9 cats with other neurological or neuromuscular disorders (ONM) and 46 neurologically normal cats (CTRL) were examined for the presence of IgG antibodies against glycolipids GM1, GM2, GD1a, GD1b, GalNAc-GD1a, GA1, SGPG, LM1, galactocerebroside and sulphatide.

Guillain-Barré Syndrome Following Zika Virus Infection Is Associated With a Diverse Spectrum of Peripheral Nerve Reactive Antibodies.

Background And Objectives: Recent outbreaks of Zika virus (ZIKV) in South and Central America have highlighted significant neurologic side effects. Concurrence with the inflammatory neuropathy Guillain-Barré syndrome (GBS) is observed in 1:4,000 ZIKV cases. Whether the neurologic symptoms of ZIKV infection are immune mediated is unclear.

Detection of Autoantibodies Using Combinatorial Glycolipid Microarrays.

Glycolipids cluster in plasma membranes to form heterogenous patches. Whereas lectins and antibodies have been conventionally viewed as binding a single oligosaccharide head group, and assayed accordingly, it is increasingly evident that cis-interactions between glycan headgroups may form unique molecular shapes that either enhance or attenuate binding of antibodies and other proteins. Herein we describe a method for assaying antibody binding to heteromeric glycolipid complexes that allows rapid, simple, inexpensive and high-throughput assessment of binding events, focusing on autoantibodies present in human serum.

Guillain-Barré Syndrome Outbreak in Peru 2019 Associated With Infection.

Objective: To identify the clinical phenotypes and infectious triggers in the 2019 Peruvian Guillain-Barré syndrome (GBS) outbreak.

Methods: We prospectively collected clinical and neurophysiologic data of patients with GBS admitted to a tertiary hospital in Lima, Peru, between May and August 2019. Molecular, immunologic, and microbiological methods were used to identify causative infectious agents.

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

Objective: To determine the clinical phenotype of Guillain-Barré syndrome (GBS) after Zika virus (ZIKV) infection, the anti-glycolipid antibody signature, and the role of other circulating arthropod-borne viruses, we describe a cohort of GBS patients identified during ZIKV and chikungunya virus (CHIKV) outbreaks in Northeast Brazil.

Methods: We prospectively recruited GBS patients from a regional neurology center in Northeast Brazil between December 2014 and February 2017. Serum and CSF were tested for ZIKV, CHIKV, and dengue virus (DENV), by RT-PCR and antibodies, and serum was tested for GBS-associated antibodies to glycolipids.

Differential binding patterns of anti-sulfatide antibodies to glial membranes.

Sulfatide is a major glycosphingolipid in myelin and a target for autoantibodies in autoimmune neuropathies. However neuropathy disease models have not been widely established, in part because currently available monoclonal antibodies to sulfatide may not represent the diversity of anti-sulfatide antibody binding patterns found in neuropathy patients. We sought to address this issue by generating and characterising a panel of new anti-sulfatide monoclonal antibodies.

Autoimmune Neurological Conditions Associated With Zika Virus Infection.

Zika virus (ZIKV) is an emerging flavivirus rapidly spreading throughout the tropical Americas. mosquitoes is the principal way of transmission of the virus to humans. ZIKV can be spread by transplacental, perinatal, and body fluids.

Inhibition of complement in Guillain-Barré syndrome: the ICA-GBS study.

The outcome of Guillain-Barré syndrome (GBS) remains unchanged since plasma exchange and intravenous immunoglobulin (IVIg) were introduced over 20 years ago. Pathogenesis studies on GBS have identified the terminal component of complement cascade as a key disease mediator and therapeutic target. We report the first use of terminal complement pathway inhibition with eculizumab in humans with GBS.

Microarray screening of Guillain-Barré syndrome sera for antibodies to glycolipid complexes.

Objective: To characterize the patterns of autoantibodies to glycolipid complexes in a large cohort of Guillain-Barré syndrome (GBS) and control samples collected in Bangladesh using a newly developed microarray technique.

Methods: Twelve commonly studied glycolipids and lipids, plus their 66 possible heteromeric complexes, totaling 78 antigens, were applied to polyvinylidene fluoride-coated slides using a microarray printer. Arrays were probed with 266 GBS and 579 control sera (2 μL per serum, diluted 1/50) and bound immunoglobulin G detected with secondary antibody.

Anti-ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.

SEE VAN DOORN AND JACOBS DOI101093/BRAIN/AWW078 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE  : In axonal forms of Guillain-Barré syndrome, anti-ganglioside antibodies bind gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-ganglioside antibodies from the cell surface so rapidly that antibody-mediated injury is attenuated.

Guillain-Barré Syndrome outbreak associated with Zika virus infection in French Polynesia: a case-control study.

Background: Between October, 2013, and April, 2014, French Polynesia experienced the largest Zika virus outbreak ever described at that time. During the same period, an increase in Guillain-Barré syndrome was reported, suggesting a possible association between Zika virus and Guillain-Barré syndrome. We aimed to assess the role of Zika virus and dengue virus infection in developing Guillain-Barré syndrome.

The Diagnostic Utility of Determining Anti-GM1: GalC Complex Antibodies in Multifocal Motor Neuropathy: A Validation Study.

Background: Multifocal motor neuropathy (MMN) is associated with IgM antibodies to GM1 ganglioside. The importance of the lipid milieu that might facilitate or inhibit antibody binding to GM1 in immunoassays is well recognised. Existing studies, using a range of different approaches, generally concur that anti-GM1 IgM antibody detection rates are improved by the addition of galactocerebroside (GalC) to the GM1 assay.

Improving the detection of IgM antibodies against glycolipids complexes of GM1 and Galactocerebroside in Multifocal Motor Neuropathy using glycoarray and ELISA assays.

Antibodies against complexes of GM1:GalC are detected in multifocal motor neuropathy. Previous studies used different techniques, explaining disparities in the results. Antibodies against GM1 and GM1:GalC with different proportions of GalC were measured with both glycoarray and ELISA in 20 multifocal motor neuropathies, and 45 controls.

The application of glycosphingolipid arrays to autoantibody detection in neuroimmunological disorders.

Humans with autoimmune peripheral neuropathies frequently harbour serum antibodies to single glycosphingolipids, especially gangliosides. Recently it has been appreciated that glycolipid and lipid complexes, formed from two or more individual species, can interact to create molecular shapes capable of being recognised by these autoantibodies whilst not binding to the single individuals. As a result of this, novel autoantibody targets have been identified.

Motor nerve terminal destruction and regeneration following anti-ganglioside antibody and complement-mediated injury: an in and ex vivo imaging study in the mouse.

Both the neural and glial components of the neuromuscular junction (NMJ) have been identified as potential sites for anti-ganglioside antibody (Ab) binding and complement-mediated injury in murine models for the human peripheral nerve disorder Guillain-Barré syndrome (GBS). Some patients suffering from the acute motor axonal neuropathy (AMAN) forms of GBS recover very rapidly from paralysis; it has been proposed that in these cases the injury was restricted to the distal motor axons and nerve terminals (NTs) which are able to regenerate over a very short time-frame. To test this hypothesis, the ventral neck muscles of mice (n=45) expressing cytosolic fluorescent proteins in their axons (CFP) and Schwann cells (GFP) were subjected to a single topical application of anti-ganglioside Ab followed by a source of complement.

Anti-GD1a antibodies activate complement and calpain to injure distal motor nodes of Ranvier in mice.

The motor axonal variant of Guillain-Barré syndrome is associated with anti-GD1a immunoglobulin antibodies, which are believed to be the pathogenic factor. In previous studies we have demonstrated the motor terminal to be a vulnerable site. Here we show both in vivo and ex vivo, that nodes of Ranvier in intramuscular motor nerve bundles are also targeted by anti-GD1a antibody in a gradient-dependent manner, with greatest vulnerability at distal nodes.

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice.

Anti-GM1 ganglioside autoantibodies are used as diagnostic markers for motor axonal peripheral neuropathies and are believed to be the primary mediators of such diseases. However, their ability to bind and exert pathogenic effects at neuronal membranes is highly inconsistent. Using human and mouse monoclonal anti-GM1 antibodies to probe the GM1-rich motor nerve terminal membrane in mice, we here show that the antigenic oligosaccharide of GM1 in the live plasma membrane is cryptic, hidden on surface domains that become buried for a proportion of anti-GM1 antibodies due to a masking effect of neighboring gangliosides.

C5 inhibitor rEV576 protects against neural injury in an in vitro mouse model of Miller Fisher syndrome.

Guillain-Barré syndrome and its clinical variants, including the anti-GQ1b ganglioside-mediated Miller Fisher syndrome (MFS), comprise the world's leading cause of acute neuromuscular paralysis. Presently, no specific drug therapies exist. The complement cascade, which is activated in these patients, forms an attractive drug target.