gq1b-ganglioside and Peripheral-Nervous-System-Diseases

The recent literature about autoimmune peripheral neuropathies has been dominated by the discovery of antibodies to a variety of glycosphingolipids. Gangliosides are important carbohydrate determinants for autoimmune activity, and several studies have suggested that serum antibodies against gangliosides are responsible for some forms of acute and chronic neuropathy syndromes. However, this view is disputable, and despite substantial progress in understanding the potential pathogenic effects of antiganglioside antibodies, many central issues remain unresolved across the whole pathogenic process. Miller Fisher syndrome has been classified as a variant of Guillain-Barré syndrome that comprises the clinical triad of ataxia, areflexia, and ophthalmoplegia. It has been considered the archetypal antiganglioside antibody-mediated human neuropathy because anti-GQ1b ganglioside antibody is detected in most patients with Miller Fisher syndrome, decays rapidly with clinical recovery, and is not found in normal and disease control serum samples. The only other case in which this antibody is found is in patients with related conditions, which might share the same pathogenic mechanism, such as Bickerstaff brainstem encephalitis. The strength of this close serologic-clinical association is such that measurement of anti-GQ1b antibody in suspected cases of Miller Fisher syndrome is a useful diagnostic marker for clinicians. This article reviews the occurrence, the pathophysiologic role, and the clinical background of anti-GQ1b ganglioside antibody in Miller Fisher syndrome and related disorders.

Topics: Animals; Autoantibodies; Gangliosides; Humans; Peripheral Nervous System Diseases

Monolithic columns containing ganglioside GM2 and GM3 mimics were prepared for selective removal of serum anti-ganglioside antibodies from patients with acute and chronic immune-mediated neuropathies. ELISA results demonstrated that anti-GM2 IgM antibodies in human sera and a mouse monoclonal anti-GM2 antibody were specifically and selectively adsorbed by monolithic GM2 mimic columns and not by blank monolithic columns or monolithic GM3 mimic columns. In control studies, serum antibodies against the ganglioside GQ1b from another neuropathy patient were not depleted by monolithic GM2 mimic columns. Fluorescence microscopy with FITC-conjugated anti-human immunoglobulin antibodies showed that the immobilized ganglioside mimics were evenly distributed along the column. The columns were able to capture ∼95% of the anti-GM2 antibodies of patients after only 2 min of incubation. A monolithic column of 4.4 μL can deplete 28.2 μL of undiluted serum. These columns are potential diagnostic and therapeutic tools for neuropathies related to anti-ganglioside antibodies.

Topics: Adsorption; Animals; Antibodies, Monoclonal; Chemistry, Pharmaceutical; Drug Design; Enzyme-Linked Immunosorbent Assay; Fluorescein-5-isothiocyanate; G(M2) Ganglioside; Gangliosides; Humans; Immunoglobulin M; Mice; Microscopy, Fluorescence; Peripheral Nervous System; Peripheral Nervous System Diseases

We report a case of Fisher syndrome accompanied by ocular flutter. A 19-year-old man presented with diplopia and vertigo, associated with preceding symptoms of common cold. Since symmetric weakness of abduction in both eyes, truncal ataxia, diminution of tendon reflexes, and gaze nystagmus were noted, he was diagnosed as having Fisher syndrome. Ocular flutter also was noticed during horizontal gaze. Serum anti-GQ1b antibody and anti-GM1 antibody were detected. He was followed without therapy and the symptoms resolved. The accompanying ocular flutter may suggest that a central nervous system disorder may also be present in Fisher syndrome.

Topics: Autoantibodies; Biomarkers; Central Nervous System Diseases; G(M1) Ganglioside; Gangliosides; Humans; Male; Miller Fisher Syndrome; Ocular Motility Disorders; Peripheral Nervous System Diseases; Young Adult

Thirty-two consecutive adult celiac disease (CD) patients (pts), complaining of peripheral neuropathy (12 pts), autonomic dysfunction (17 pts), or both (3 pts), were evaluated to assess the presence of neurological damage (by clinical neurological evaluation and electrophysiological study) and antineuronal antibodies and to assess the effect of a gluten-free diet (GFD) on the course of the neurological symptoms and on antineuronal antibodies. At entry, 12 of 32 (38%) pts showed signs and symptoms of neurological damage: 7 of 12 (58%), peripheral neurological damage; 3 of 12 (25%), autonomic dysfunction; and 2 (17%), both peripheral neurological damage and autonomic dysfunction. The overall TNS score was 105 at entry. Anti-GM1 antibodies were present in 5 of 12 (42%) pts: 3 showed peripheral neurological damage and 2 showed both peripheral neurological damage and autonomic dysfunction. One year after the GFD was started, histological lesions were still present in only 10 of 12 (83%) pts. TNS score was 99, 98, 98, and 101 at the 3rd, 6th, 9th, and 12th month after the GFD was started, so it did not improve throughout the follow-up. None of the pts showed disappearance of antineuronal antibodies throughout the follow-up. We conclude that adult CD patients may show neurological damage and presence of antineuronal antibodies. Unfortunately, these findings do not disappear with a GFD.

Topics: Adolescent; Adult; Aged; Antibodies; Autonomic Nervous System Diseases; Celiac Disease; Cohort Studies; Female; G(M1) Ganglioside; Gangliosides; Gliadin; Humans; Male; Middle Aged; Peripheral Nervous System Diseases

Serum IgG antibody against LM1, the predominant ganglioside in the human peripheral nerve myelin, was found in 7 out of 140 patients with Guillain-Barré syndrome (GBS) in the acute phase, 1 out of 33 patients with chronic inflammatory demyelinating polyneuropathy (CIDP), and 2 out of 47 patients with Miller Fisher syndrome (MFS). Anti-LM1 IgM antibody was detected only in 2 patients, each with GBS and MFS. The clinical and electrophysiological features of the seven GBS patients with anti-LM1 IgG antibody in the serum were investigated. Six patients recovered to grade 1 within one month of the onset of neuropathy. Electrophysiological studies revealed demyelination in five patients, of which one had axonal damage in addition, whereas sufficient evidence of demyelination or axonal degeneration was not observed in the remaining two. Five had a respiratory tract infection before the onset of neuropathy, and also had serum anti-GQ1b IgG antibody. IgG antibody against LM1 might be involved in the pathogenetic mechanisms of GBS, as a possible demyelinating factor. Presence of both anti-GQ1b and anti-LM1 antibodies may be associated with some infectious agent(s) affecting the respiratory tract.

Topics: Antibodies, Bacterial; Autoantibodies; Campylobacter jejuni; Chromatography, Thin Layer; Gangliosides; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Miller Fisher Syndrome; Myelin Sheath; Peripheral Nerves; Peripheral Nervous System Diseases; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating; Respiratory Tract Infections

We studied the frequency, fine specificity and clinical correlate of anti-GQ1b IgG and IgM antibodies in 216 patients with neuropathy including three with Miller Fisher syndrome (MFS), 73 with Guillain-Barré syndrome (GBS), 99 with neuropathy associated with IgM monoclonal gammopathy (PN+IgM) and 41 with other neuropathies, and compared the data with 92 disease or normal controls. We found high (>1/100) anti-GQ1b IgG titers in all three MFS patients and in two GBS patients (2.7%) with ophthalmoplegia and ataxia, while high anti-GQ1b IgM were only found in two patients with a chronic demyelinating sensorimotor neuropathy associated with IgMkappa monoclonal gammopathy (2%). By overlay HPTLC, IgG antibodies in MFS and GBS either selectively reacted with GQ1b or also bound to GD3, and less intensely to GD1b, while IgM antibodies from both patients with PN+IgM also strongly reacted with GD1b and, in one, with GD3 and GT1b. The constant association of anti-GQ1b antibodies with dysimmune neuropathies and the correlation between their isotype, fine specificity and clinical presentation, support a possible pathogenetic link between these antibodies and the neuropathy.

Topics: Antibody Formation; Antibody Specificity; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; Gangliosides; Humans; Immunoglobulin M; Peripheral Nervous System Diseases; Polyradiculoneuropathy

Topics: Ataxia; Autoantibodies; Autoantigens; Autoimmune Diseases; Ganglia, Sensory; Gangliosides; Glycolipids; Humans; Peripheral Nervous System Diseases