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Intravenous immunoglobulins (IVIg) are standard treatment for Guillain-Barré syndrome (GBS). Their exact mechanisms of action are versatile and not fully understood. One possible mechanism is neutralization of circulating autoantibodies via binding to anti- idiotypic antibodies forming idiotype-anti-idiotype dimeric IgG immune complexes. To examine the role of immune complex formation as mechanism of action for IVIg in GBS, 34 C57Bl/6 mice were either treated with anti-ganglioside antibodies and IVIg or IVIg and PBS alone, whereas eight additional mice were treated either with anti-ganglioside autoantibodies and IVIg or anti-ganglioside autoantibodies alone. Subsequently IgG dimer formation was assessed by high performance liquid chromatography (HPLC) and enzyme- linked immunosorbent assay (ELISA). In addition, IgG dimer formation was measured in sera of eight GBS patients who were treated with IVIg. In mice, a significant increase of dimeric IgG after administration of anti-ganglioside antibodies and IVIg could be observed. Re-monomerized IgG dimers showed immunoreactivity against gangliosides and serum immunoreactivity was significantly reduced after IVIg infusion. Likewise also in GBS patients, IgG dimer formation could be detected after IVIg treatment. Our data indicate that dimeric IgG immune complexes contain anti-idiotypic antibodies and provide proof of concept that IVIg treatment in GBS results in measurable amounts of IgG dimers. Larger patient cohorts are needed to evaluate serum IgG dimer increase as a possible marker for treatment response in GBS. Graphical Abstract Mechanism of action: Intravenous immunoglobulins (IVIg) and anti-ganglioside antibodies form dimeric IgG immune complexes, preventing axonal damage in Guillain-Barré Syndrome.

Background: Unlike for acute immune-mediated neuropathies (IN), anti-ganglioside autoantibody (aGAAb) testing has been recommended for only a minority of chronic IN yet. Thus, we used a multiplex semi-quantitative line immunoassay (LIA) to search for aGAAb in chronic-inflammatory demyelinating polyneuropathy (CIDP) and its clinical variants., Methods: Anti-GAAb to 11 gangliosides and sulfatide (SF) were investigated by LIA in 61 patients with IN (27 typical CIDP, 12 distal-acquired demyelinating polyneuropathy, 6 multifocal-acquired demyelinating sensory/motor polyneuropathy, 10 sensory CIDP, 1 focal CIDP and 5 multifocal-motoric neuropathy), 40 with other neuromuscular disorders (OND) (15 non-immune polyneuropathies, 25 myasthenia gravis), 29 with multiple sclerosis (MS) and 54 healthy controls (HC)., Results: In contrast to IgG, positive anti-GAAB IgM against at least one ganglioside/SF was found in 17/61 (27.9%) IN compared to 2/40 (5%) in OND, 2/29 MS (6.9%) and 4/54 (7.4%) in HC (p=0.001). There was a statistically higher prevalence of anti-sulfatide (aSF) IgM in IN compared to OND (p=0.008). Further, aGM1 IgM was more prevalent in IN compared to OND and HC (p=0.009) as well as GD1b in IN compared to HC (p<0.04). The prevalence of aGM1 IgM in CIDP was lower compared to in multifocal motor neuropathy (MMN) (12% vs. 60%, p=0.027). Patients showing aSF, aGM1 and aGM2 IgM were younger compared to aGAAb negatives (p<0.05). Patients with aSF IgM positivity presented more frequently typical CIDP and MMN phenotypes (p<0.05, respectively)., Conclusions: The aGAAb LIA revealed an elevated frequency of at least one aGAAb IgM in CIDP/MMN patients. Anti-SF, aGM1 and aGM2 IgM were associated with younger age and anti-SF with IN phenotypes.

Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used. NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown. Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Guillain-Barré Syndrome (GBS) is a demyelinating polyneuropathy resulting in sensory, motor and autonomic symptoms. The severity of the disease can range from mild to severe but it is classically described as an ascending demyelinating process. Initially thought to be the sequelae of a bacterial or viral infection, the clinical symptoms of post-infective GBS can present up to 4 weeks after sentinel injury. A rarely defined post-surgical GBS has been since described after major cranial, cardiothoracic and gastro-intestinal surgery. Post traumatic GBS is an even more unusual presentation with very few cases reported in contemporary academic literature. We present a case of GBS presenting two weeks after non-operative traumatic brain injury (TBI) and a review of the literature.

Natura non facit saltus (Latin for "nature does not make jumps") is a maxim expressing the idea that natural things and properties change gradually, in a continuum, rather than suddenly. In biomedical sciences, for taxonomic purposes, we make jumps that emphasize differences more than similarities. Among the dysimmune neuropathies, 2 disorders, characterized by the presence of antibodies to gangliosides GM1 and GD1a and a peculiar, exclusive motor involvement, have been identified: acute motor axonal neuropathy (AMAN) and multifocal motor neuropathy (MMN). However, anti-GM1 or -GD1a antibodies are also associated with acute motor and sensory axonal motor neuropathy (AMSAN). We review the results of recent clinical and experimental studies showing that AMAN and MMN are not exclusively motor. We discuss the possible explanations for the greater resistance of sensory fibers to antibody attack to finally suggest that AMAN, AMSAN, and MMN belong to a continuous spectrum with a common pathophysiological mechanism., (Copyright © 2013 Wiley Periodicals, Inc.)

Background and Aims: This study aimed to identify the clinical characteristics and electrodiagnostic subtypes of Guillain‐Barré syndrome (GBS) in Istanbul. Methods: Patients with GBS were prospectively recruited between April 2019 and March 2022 and two electrodiagnostic examinations were performed on each patient. The criteria of Ho et al., Hadden et al., Rajabally et al., and Uncini et al. were compared for the differentiation of demyelinating and axonal subtypes, and their relations with anti‐ganglioside antibodies were analyzed. Results: One hundred seventy‐seven patients were included, 69 before the coronavirus disease 2019 pandemic (April 2019–February 2020) and 108 during the pandemic (March 2020–March 2022), without substantial changes in monthly frequencies. As compared with the criteria of Uncini et al., demyelinating GBS subtype diagnosis was more frequent according to the Ho et al. and Hadden et al. criteria (95/162, 58.6% vs. 110/174, 63.2% and 121/174, 69.5%, respectively), and less frequent according to Rajabally et al.'s criteria (76/174, 43.7%). Fourteen patients' diagnoses made using Rajabally et al.'s criteria were shifted to the other subtype with the second electrodiagnostic examination. Of the 106 analyzed patients, 22 had immunoglobulin G anti‐ganglioside antibodies (14 with the axonal subtype). They had less frequent sensory symptoms (54.5% vs. 83.1%, p = 0.009), a more frequent history of previous gastroenteritis (54.5% vs. 22.9%, p = 0.007), and a more severe disease as compared with those without antibodies. Interpretation: Serial electrodiagnostic examinations are more helpful for accurate subtype diagnosis of GBS because of the dynamic pathophysiology of the disease. We observed no significant increase in GBS frequency during the pandemic in this metropolis. [ABSTRACT FROM AUTHOR]

Preceding infection with Campylobacter jejuni (Cj) occurs in approximately 30% of patients with Guillain–Barre syndrome (GBS), and the risk of GBS following Cj infection is increased by 77 to 100-fold. GBS is most often of the axonal subtype and is thought to be mediated by IgG antibodies to peripheral nerve gangliosides that are cross reactive with oligosaccharides in the Cj lipopolysaccharides (LPS). The antibodies are thought to be induced by molecular mimicry, where immune reactivity to a cross reactive epitope in the infectious organism and normal tissue can cause autoimmune disease. Clonally restricted IgM antibodies that react with the same oligosaccharides in gangliosides and Cj-LPS are associated with chronic neuropathies of otherwise similar phenotypes. The anti-ganglioside antibodies in GBS are of the IgG1 and IgG3 subclasses, indicating T-cell reactivity to the same antigens that could help disrupt the blood–nerve barrier. Cj infection can activate multiple innate and adoptive pro-inflammatory pathways that can overcome immune tolerance and induce autoimmunity. Elucidation of the specific immune mechanisms involved in the development of the autoantibodies and neuropathy would help our understanding of the relation between infection and autoimmunity and aid in the development of more effective preventive interventions and therapies. [ABSTRACT FROM AUTHOR]

Abstract: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most difficult manifestations of lupus to diagnose. Measurement of serum brain antibodies has contributed to early diagnosis and management of NPSLE before development of a debilitating disease. We aimed to assess the value of serum anti-ganglioside M1 antibodies in prediction of NPSLE, in comparison to other antibodies used in routine laboratory diagnosis of NPSLE. In addition, we are the first to study the relationship between these antibodies and cognitive function in lupus patients. Serum anti-ganglioside M1, anti-ribosomal P protein and anti-cardiolipin antibodies were measured in 30 lupus patients without clinical evidence of NPSLE, aged 8–16years, and 30 healthy matched-subjects. Patients were followed-up clinically by monthly neuropsychiatric evaluation and assessment of cognitive function for 12months. Twelve patients developed neuropsychiatric manifestations during follow-up. Of those patients, 83.3%, 50% and 16.7% were seropositive for anti-ganglioside M1, anti-ribosomal P and anti-cardiolipin antibodies, respectively at the time of initial evaluation before clinical presentation of NPSLE. There was a significant positive association between anti-ganglioside seropositivity and cognitive dysfunction (P<0.001). In addition, anti-ganglioside seropositivity had a significant risk for association with cognitive dysfunction (odds ratio: 36; 95% CI: 4.3–302.8). Conclusions: Serum anti-ganglioside M1 antibodies had a higher predictive value for NPSLE than other antibodies used in routine laboratory diagnosis of this disease. Thus, they may be reliable parameters for early diagnosis and management of NPSLE before clinical manifestations ensue. In addition, anti-ganglioside M1 antibodies may play a role in cognitive dysfunction found in some lupus patients. [ABSTRACT FROM AUTHOR]