ganglioside--gd1b and Nervous-System-Diseases

Topics: Animals; Autoantibodies; Chronic Disease; Gangliosides; Glycolipids; Guillain-Barre Syndrome; Humans; Immunoglobulin G; Immunoglobulin M; Nerve Growth Factors; Nervous System Diseases; Paraproteinemias

Evidence of immune-mediated neurological syndromes associated with the severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection is limited. We therefore investigated clinical, serological and CSF features of coronavirus disease 2019 (COVID-19) patients with neurological manifestations.. Consecutive COVID-19 patients with neurological manifestations other than isolated anosmia and/or non-severe headache, and with no previous neurological or psychiatric disorders were prospectively included. Neurological examination was performed in all patients and lumbar puncture with CSF examination was performed when not contraindicated. Serum anti-gangliosides antibodies were tested when clinically indicated.. Of the 349 COVID-19 admitted to our center between March 23rd and April 24th 2020, 15 patients (4.3%) had neurological manifestations and fulfilled the study inclusion/exclusion criteria. CSF examination was available in 13 patients and showed lymphocytic pleocytosis in 2 patients: 1 with anti-contactin-associated protein 2 (anti-Caspr2) antibody encephalitis and 1 with meningo-polyradiculitis. Increased serum titer of anti-GD1b antibodies was found in three patients and was associated with variable clinical presentations, including cranial neuropathy with meningo-polyradiculitis, brainstem encephalitis and delirium. CSF PCR for SARS-CoV-2 was negative in all patients.. In SARS-Cov-2 infected patients with neurological manifestations, CSF pleocytosis is associated with para- or post-infectious encephalitis and polyradiculitis. Anti-GD1b and anti-Caspr2 autoantibodies can be identified in certain cases, raising the question of SARS-CoV-2-induced secondary autoimmunity.

Topics: Adult; Aged; Aged, 80 and over; Antibodies; COVID-19; Delirium; Encephalitis; Female; Gangliosides; Humans; Leukocytosis; Male; Membrane Proteins; Middle Aged; Nerve Tissue Proteins; Nervous System Diseases; Neurologic Examination; Radiculopathy; Spinal Puncture

We report on a 54-year-old man with a sensory-motor polyneuropathy associated with a biclonal IgM-kappa gammopathy, which reacted with the ganglioside GD1b. Examination of nerve biopsy specimens showed some reduction in the density of myelinated fibers and axonal degeneration with a loss of large fibers and a relative increase in the density of small fibers. Immunodetection on thin-layer chromatography of the glycolipid antigens showed strong reactivity of the patient's serum IgM-kappa with GD1b ganglioside and weak binding to GD1a. biclonal IgM antibodies did not react with GM1, asialo-GM1, GT1b, GD2, or GD3. Indirect immunofluorescence staining showed binding of IgM-kappa mainly in a crescent-like pattern on the internal side of myelin sheaths, which could correspond either to an enlarged periaxonal (adaxonal) space or to the internal mesaxon or to both. The immunostaining was abolished after absorption of the serum with GD1b.

Topics: Antigens; Blotting, Western; Epitopes; Gangliosides; Humans; Immunoglobulin M; Male; Middle Aged; Motor Activity; N-Acetylneuraminic Acid; Nervous System Diseases; Peroneal Nerve; Sensation; Sialic Acids; Staining and Labeling

Anti-GM1 antibodies were measured in 22 patients with the Guillain-Barré syndrome (GBS) and compared with anti-GM1 antibody activity in patients with other neurological or immunological diseases and in normal subjects. Four out of 22 patients with GBS had raised IgM, IgG, or IgA anti-GM1 antibody activities. All four patients were tetraparetic with only minimal or no sensory deficit. Three of the patients had highly raised antibody activity and showed severe residual deficits, while of the remaining patients with GBS, only one remained severely affected. One patient had anti-GM1 antibodies specific for GM1, whereas the other three patients showed antibody activity with asialo-GM1 or GD1b. The presence of anti-GM1 antibodies may define a subgroup of patients with GBS who have a poor prognosis.

Topics: Adolescent; Adult; Aged; Antibody Specificity; Autoantibodies; Child; Diagnosis, Differential; Female; G(M1) Ganglioside; Gangliosides; Glycosphingolipids; Humans; Immunoglobulin M; Male; Middle Aged; Nervous System Diseases; Neurologic Examination; Polyradiculoneuropathy

We report a patient with a relapsing form of the acute sensory neuropathy syndrome associated with IgM-kappa type monoclonal gammopathy of undetermined significance. He rapidly developed marked sensory ataxia without weakness following an upper respiratory tract infection at age 44. The symptoms reached their maximum in a few days, followed by subsequent gradual improvement over a few weeks. However, unsteady gait remained as a chronic deficit. Stepwise progression of his symptoms occurred over 15 years with 10 similar relapses. Sensory nerve conduction studies showed the absence of action potentials, and sural nerve biopsy revealed the marked loss of large myelinated fibers. The patient's serum had an extremely high titer of an IgM monoclonal antibody directed against gangliosides GD2, GD1b, GT1b, and GQ1b.

Topics: Acute Disease; Adult; Carbohydrate Sequence; Gangliosides; Humans; Immunoglobulin M; Male; Molecular Sequence Data; Nervous System Diseases; Recurrence; Sensation

Antibodies to gangliosides were detected in sera from three of 19 patients with chronic inflammatory polyneuropathy (CIP) by a thin-layer chromatogram overlay technique. All three of the patients fell into a clinical subset of the group that had multifocal motor neuropathy, and in all three patients the antibodies reacted with GM1 ganglioside. However, the fine specificities of the antibodies differed as demonstrated by cross-reactivity with different gangliosides in each of the three patients. The antibodies in patient 1 reacted with GM1, GD1b, and asialo-GM1 suggesting that the terminal Gal(beta 1-3)GalNAc moiety that is common to these three glycolipids is an important part of the epitope(s). This was confirmed by showing reactivity of the antibodies with Gal(beta 1-3)GalNAc conjugated to bovine serum albumin. Patient 2 had antibodies that did not react with GD1b, but cross-reacted with GM2 ganglioside suggesting that the epitope(s) involved the inner portion of the oligosaccharide moiety that is shared between GM1 and GM2. Patient 3 had antibodies that reacted with GM1 and asialo-GM1, but they did not cross-react with either GD1b or GM2. These results provide further evidence for a relationship between motor nerve syndromes and anti-GM1 antibodies and also suggest that GM1 could be a principal target antigen since other reactive gangliosides differed among the patients. However, the possible pathogenic effects of anti-GM1 antibodies on motor nerves remain to be established.

Topics: Antibodies; Antibody Specificity; Chromatography, Thin Layer; Cross Reactions; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Glycosphingolipids; Humans; Nervous System Diseases; Neuromuscular Diseases; Polyneuropathies