g(m1)-ganglioside and Nervous-System-Diseases

Topics: Autoantibodies; Autoimmune Diseases; G(M1) Ganglioside; Gangliosides; Humans; Nervous System Diseases

We performed a meta-analysis on the diagnostic value of IgM anti-GM1 antibodies. The reported frequencies of IgM anti-GM1 antibodies ranged from 0 to 100% for patients with multifocal motor neuropathy (MMN), from 0 to 33% in the Guillain-Barré syndrome, from 0 to 65% in amyotrophic lateral sclerosis (ALS), from 0 to 77% in chronic inflammatory demyelinating neuropathy, and from 0 to 81% in lower motor neuron disease (LMND). However, using funnel graphs and a chi-square test we determined that the method of ELISA was the most important factor explaining these differences. After allowing for two factors--the use of detergent and the duration and temperature of serum incubation-studies became homogeneous in all but the LMND group of method A (no detergent, duration of serum incubation 5 hours) and the ALS group of method B (no detergent, duration of serum incubation at least 12 hours [overnight]). Since the anti-GM1 antibody assay serves to confirm clinical suspicion of MMN rather than to exclude the disease, specificity is more important than sensitivity. ELISA methods that do not use detergent and that incubate serum overnight resulted in a specificity of 90% and sensitivity of 38% in the comparison of MMN and LMND. With these values we calculated incremental ruling-in and ruling-out gain curves. Prior probabilities between 20 and 60% for having MMN changed to post-test probabilities between 50 and 85%, which is of clinical importance. In conclusion, ELISA is a useful diagnostic test to demonstrate IgM anti-GM1 antibodies provided the methods do not use detergent and do incubate serum overnight.

Topics: Antibodies; G(M1) Ganglioside; Humans; Immunoglobulin M; Motor Neuron Disease; Nervous System Diseases

There is increasing evidence that multifocal motor neuropathy (MMN) and some lower motor neuron (LMN) syndromes are immune-mediated and treatable. The frequent occurrence of high titers of anti-GM1 antibodies in these motor neuropathies raised hopes that serum testing would provide useful diagnostic information. Unfortunately, in routine practice, simple quantification of IgM binding to GM1 ganglioside has proved to be a test with poor sensitivity and specificity. We have found that much greater sensitivity and specificity for MMN and LMN syndromes can be obtained by determining serum antibody binding to panels of antigens, such as GM1, histone H3, and NP-9. These results suggest that combined measurement of serum antibody binding to GM1 and other antigens can provide tests that are useful in the diagnosis and management of motor neuropathy syndromes.

Topics: Antibodies; Antigen-Antibody Reactions; Demyelinating Diseases; G(M1) Ganglioside; Humans; Motor Neuron Disease; Nervous System Diseases

Multifocal motor neuropathy (MMN) is a disorder with a highly characteristic clinical picture and one which is defined by a specific electrodiagnostic abnormality, namely, multifocal conduction block which is confined to motor axons. Sensory axons which traverse segments of severe or even complete motor conduction block conduct normally. A proportion of patients with MMN also have elevated levels of antibodies to GM1 ganglioside. However, about one half of MMN patients lack elevated levels of these antibodies and many others have only modest elevations, to a degree often seen in other neurological and even non-neurological disorders. Furthermore, clinical and electrophysiological improvement of MMN in response to treatment with high dose intravenous immunoglobulin is achieved in the absence of any change in antiglycolipid levels. Injection of serum from patients with MMN and elevated GM1 antibody levels produces demyelination in recipient rat nerves, suggesting a pathogenetic role for these antibodies in demyelination. However, sera of patients with identical antibody titers in other motor system diseases produced no demyelination, suggesting that the demyelinating factor resides in some other serum fraction. At present, there is insufficient evidence to support the contention that these antibodies play a critical pathogenetic role in MMN. Until more evidence is available it is important to define MMN on the basis of a characteristic clinical picture and a unique electrodiagnostic abnormality rather than on a pattern of serum antibodies.

Topics: Animals; Antibodies; Autoimmune Diseases; G(M1) Ganglioside; Glycolipids; Humans; Motor Neuron Disease; Nervous System Diseases; Rats

Topics: Antibodies; Diagnosis, Differential; G(M1) Ganglioside; Humans; Motor Neurons; Movement Disorders; Nervous System Diseases; Neural Conduction; Neuromuscular Diseases

Increased titers of IgM antibodies that react with carbohydrate epitopes on GM1 are present in some patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without conduction block. Therapeutic reduction of antibody concentrations can result in clinical improvement, suggesting that the antibodies may be pathogenic. The anti-GM1 antibodies react with carbohydrate epitopes, which are shared by several other glycolipids and glycoproteins in the central and peripheral nervous system. The antibodies might exert their effects at a number of sites, depending on the topographical distribution of the target antigens and on their accessibility. B-cells that express anti-GM1 antibodies are present at birth and are normally suppressed or rendered anergic. Under some circumstances, however, they might be activated to secrete autoantibodies that cause autoimmune neuropathy.

Topics: Animals; Autoantibodies; G(M1) Ganglioside; Humans; Nervous System Diseases

Two very high titer polyclonal antibodies against two ganglioside antigens, GM1 and GD1a, have been raised in New Zealand white rabbits using a homogeneous suspension of the highly purified antigens in Keyhole Limpet Hemocyanin and Freund's adjuvant. The antisera were prepared over a period of 6 months with repeated injections of the ganglioside suspension, followed by an intravenous injection of the purified ganglioside solution, and collecting the serum (approximately 50 ml) at defined time intervals. The GM1-antibody, thus prepared, showed a cross reactivity toward GDlb and asialo-GM1 (GA1), while the GDla-antibody reacted with GD1a, GM1 and GA1 and GD1b as determined by immuno-overlay and ELISA methods. The titer for GM1 antiserum, determined by'ELISA, was greater than 1/10,000 dilution while the titer for GD1a antibody was greater than 1/5000 dilution. No neurological or behavioral abnormality was observed during the period of antiserum production. To evaluate any likely pathological damage caused by such a high titer ganglioside-antibody, autopsy of CNS as well PNS tissues from the rabbits were carried out after the final bleeding. No obvious pathological changes, including demyelination, were noted in any of the four rabbits. These observations cast doubt as to the direct effect of anti-ganglioside antibody induced neurological and pathological disorders.

Topics: Animals; Antibodies; Cross Reactions; Enzyme-Linked Immunosorbent Assay; Freund's Adjuvant; G(M1) Ganglioside; Gangliosides; Hemocyanins; Immunohistochemistry; Nervous System Diseases; Rabbits

To develop a rapid assay for the detection and measurement of anti-GM(1) ganglioside antibodies in patients with neuropathy, using a surface plasmon resonance-based biosensor.. Elevated levels of anti-GM(1) ganglioside antibodies are observed in patients with acute and chronic motor neuropathies. Assays for detecting anti-GM(1) antibodies in serum are increasingly being used to help the physician in the evaluation of these patients.. Antigens were immobilized by adsorption of GM(1) (active) and GM(2) (control) gangliosides onto a dextran-based sensor chip which is in contact with a flow cell carrying the sample. Interaction of specific antibodies directed against GM(1) with the ganglioside-coated sensor chip caused a change in refractive index at the surface of the chip, which was detected by an optical sensor, using the phenomenon of surface plasmon resonance. Sera from patients and healthy individuals were analyzed by the new assay and results were compared with those from ELISA. Anti-GM(1) antibody isotype was identified by using a secondary antibody.. The binding of anti-GM(1) antibodies to the immobilized GM(1) was observed in real time after reference subtraction of the response from GM(2) control. The response was proportional to antibody concentration. The assay exhibited high specificity for sera from patients with multifocal motor neuropathy and Guillain-Barré syndrome with antibodies against GM(1).. The surface plasmon resonance biosensor assay offers a rapid system for directly measuring antibody levels in serum without the use of any labels, while comparing favorably with the ELISA system in sensitivity and specificity.

Topics: Antibodies, Anti-Idiotypic; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Nervous System Diseases; Surface Plasmon Resonance; Time Factors

Highly elevated titers of serum anti-GM1 ganglioside antibodies are closely associated with multifocal motor neuropathy, but low titers are commonly present in normal individuals or other diseases. Current systems for measuring anti-GM1 antibodies utilize the enzyme-linked immunosorbent assay (ELISA), in which serum dilutions are tested for binding to excess antigen immobilized on the surface of microwells. The ELISA system, however, is relatively time consuming, labor intensive, and costly, in addition to being prone to methodological variability. We have developed a novel agglutination assay for the detection of anti-GM1 antibodies, utilizing GM1 ganglioside-coated latex beads. In contrast to the ELISA system, antibody titers may be quantified by testing for agglutination using latex beads coated with decreasing amounts of antigen. The agglutination assay compares favorably to the ELISA system in sensitivity and specificity, but is considerably less costly and takes only a few minutes to perform.

Topics: Amyotrophic Lateral Sclerosis; Antibodies; Demyelinating Diseases; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Latex Fixation Tests; Miller Fisher Syndrome; Nervous System Diseases; Reproducibility of Results; Sensitivity and Specificity

The occurrence and role of autoantibodies to gangliosides and other lipid-containing components of the central nervous system in Multiple Sclerosis (MS) are unsettled. Using sensitive ELISAs, we measured IgG and IgM antibody titers and absorbances to the three major gangliosides GD1a, GD1b and GM1, and to sulfatides, cardiolipin and myelin proteins in paired serum and cerebrospinal fluid (CSF) from patients with untreated MS, optic neuritis (ON), acute aseptic meningo-encephalitis (AM) and other neurological diseases (OND). Twenty-three per cent of 30 MS (P<0.04) and 18% of 32 ON patients (P<0.05) presented elevated IgG antibody titers to GD1a in serum compared to 9% of patients with OND. Six (40%) of the patients with malignant MS had elevated serum IgG antibody titers to GD1a compared to one (6%) of the patients with benign MS (P<0.04). In CSF, elevated IgG antibody titers to GD1a were measured in 13% of MS and 20% of ON patients compared to 4% of patients with OND (P<0. 03 and P<0.02, respectively). The augmented IgG response to GD1a in serum also separated MS from Guillain-Barré syndrome. Compared to OND increased IgM absorbances to sulfatides and cardiolipin were observed in CSF of patients with MS, but also in AM. Elevated IgG antibody titers to myelin proteins were found more often in MS patients' serum and MS, ON and AM patients' CSF compared to OND. The data implicate that among the multitude of enhanced B-cell responses occurring in MS and ON, that directed to GD1a is common and more discriminative, and should be evaluated in future MS treatment studies.

Topics: Adult; Antibodies, Anticardiolipin; Autoantibodies; B-Lymphocytes; Cerebrovascular Disorders; Female; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin G; Immunoglobulin M; Male; Meningoencephalitis; Middle Aged; Multiple Sclerosis; Myelin Basic Protein; Nervous System Diseases; Optic Neuritis; Recurrence; Sulfoglycosphingolipids

IgA has an important function in the gastrointestinal immune system. We investigated IgA anti-ganglioside antibodies in Guillain-Barré syndrome (GBS) and Fisher's syndrome (FS) subsequent to Campylobacter jejuni enteritis. In previous studies, serological diagnosis of C. jejuni infection was based on the detection of IgG, IgA, and IgM anti-C. jejuni antibodies. Our study, however, showed that the detection of IgG anti-C. jejuni antibody alone was sufficient for the serological diagnosis of antecedent C. jejuni enteritis in GBS and FS, when the cut-off level was defined for results of sera from C. jejuni-isolated patients. Serological evidence of C. jejuni infection was found in 62 (31%) of 201 GBS patients and 12 (18%) of 65 FS patients. IgA anti-GMI antibody was detected in sera from 33 (16%) of the GBS patients, 1 (2%) of the FS patients, and none of the 46 normal control subjects. IgA anti-GM1 antibody titers were significantly higher in the GBS patients with positive C. jejuni serology than in those with negative serology (P < 0.0001) or the FS patients with positive C. jejuni serology (P = 0.007). IgA anti-GQ1b antibody was detected in sera from 18 (28%) of the FS patients, 9 (4%) of the GBS patients, and none of the normal control subjects. FS patients with positive C. jejuni serology had significantly higher titers of IgA anti-GQ1b antibody than those with negative serology (P = 0.01) or the GBS patients with positive C. jejuni serology (P < 0.0001). We conclude that anti-GM1 and anti-GQ1b IgA antibodies are closely associated with antecedent C. jejuni enteritis in GBS and FS, respectively.

Topics: Antibodies, Bacterial; Antibody Specificity; Autoantibodies; Autoimmune Diseases; Campylobacter Infections; Campylobacter jejuni; Enteritis; G(M1) Ganglioside; Gangliosides; Humans; Immunoglobulin A; Miller Fisher Syndrome; Nervous System Diseases; Polyradiculoneuropathy

IgM, IgG, IgA, and IgG subclass anti-GM1, anti-GQ1b, and anti-asialo-GM1 (anti-GA1) antibodies, respectively, were investigated by ELISA in serum from neurological and other patients. Increased anti-GM1 occurred mostly in approximately 15-35% of the cases without statistical differences; high percentages were found in Guillain-Barré syndrome (GBS) preceded by gastrointestinal infection and multifocal motor neuropathy. Roughly, IgM anti-GM1 was most frequent; however, distinct IgG and IgA reactions were found i.a. in GBS. A particular IgM anti-mono- and disialoganglioside pattern occurred in a patient with sensorimotor neuropathy and paraproteinemia. Anti-GQ1b was elevated in all Miller-Fisher patients, with some prevalence of IgG2 among IgG subclasses. Cross-reactivity of anti-GQ1b was demonstrated with Campylobacter jejuni lipopolysaccharides. Increased anti-GM1 and/or anti-GA1 was more frequent in systemic lupus erythematosus with central nervous system involvement than without. Incidence of anti-GM1 and anti-GA1 in X-adrenoleukodystrophy was relatively high. Although anti-GSL antibodies seem to have limited diagnostic value, studies of isotypes, subclass patterns, and cross-reactivities may lead to further insight into the origin of (auto) immune responses and their immunepathogenetic role in disease.

Topics: Autoantibodies; Campylobacter Infections; Campylobacter jejuni; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Gangliosides; Gastrointestinal Diseases; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin Isotypes; Immunoglobulin M; Lipopolysaccharides; Nervous System Diseases; Paraproteinemias; Polyradiculoneuropathy

Gangliosides, important constituents of the plasma membrane, are particularly abundant in the nervous system. Some patients develop Guillain-Barré syndrome after the administration of bovine brain gangliosides. We previously showed existence of molecular mimicry between GM1 ganglioside and lipopolysaccharide of Campylobacter jejuni isolated from the patients with Guillain-Barré syndrome, and that between GQ1b and C. jejuni isolated from Fisher's syndrome patients. Moreover, the anti-ganglioside antibody can cause motor nerve dysfunction in vitro. These support the pathogenic significance of anti-ganglioside antibodies. To clarify clinical utility of measurement for anti-GM1 and anti-GQ1b antibodies, we investigated sera from 429 patients with immunoneurological diseases included Fisher's syndrome, Bickerstaff's brainstem encephalitis, acute ophthalmoparesis, Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, multifocal motor neuropathy, and controls by enzyme-linked immunosorbent assay. We found very high titers of IgM anti-GM1 antibody in serum from a patient who had been diagnosed as having motor neuron disease. By further electrophysiological study, the patient was diagnosed as having multifocal motor neuropathy. Presence of high IgG anti-GM1 antibody titers was useful for supporting diagnosis of Guillain-Barré syndrome, IgG anti-GQ1b antibody was detected in patients who had paresis of extraocular muscles in Fisher's syndrome, Guillain-Barré syndrome, Bickerstaff's brainstem encephalitis, and acute ophthalmoparesis. This study showed that the measurement for anti-GM1 and anti-GQ1b antibodies are very useful.

Topics: Adolescent; Adult; Autoantibodies; Female; G(M1) Ganglioside; Gangliosides; Humans; Middle Aged; Miller Fisher Syndrome; Nerve Growth Factors; Nervous System Diseases; Polyradiculoneuropathy

The group of patients with Guillain-Barr'e syndrome (GBS) is very heterogenous with regard to antecedent infections, immunological parameters, clinical manifestations, and response to treatment. In this study, the presumed pathogenic factors anti-GM1 antibodies and Campylobacter jejuni infections were related to the clinical characteristics. Serum from 154 patients with GBS, 63 patients with other neurological diseases (OND), and 50 normal controls (NC) were tested for the presence of antibodies against GM1 and C. jejuni. Anti-GM1 antibodies were detected in 31 (20%) GBS patients, 5 (8%) OND patients, and in none of the NC. Evidence for a recent C. jejuni infection was found in 49 (32%) GBS patients and less often in OND patients (11%) or NC (8%). In GBS patients, the presence of anti-GM1 antibodies was significantly associated with C. jejuni infections. The subgroup of GBS patients with anti-GM1 antibodies suffered more often from a rapidly progressive and more severe neuropathy with predominantly distal distribution of weakness, without deficits of cranial nerves or sensory disturbances. The subgroup with C. jejuni infection also more often had a severe pure motor variant of GBS. Recovery of the patients with anti-GM1 antibodies and C. jejuni infections was not as good after plasma exchange compared with intravenous immunoglobulins.

Topics: Antibodies; Campylobacter Infections; Campylobacter jejuni; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Nervous System Diseases; Plasma Exchange; Polyradiculoneuropathy; Random Allocation; Retrospective Studies

Anti-fucosyl-GM1 ganglioside antibodies were detected in sera of five persons: four patients with autoimmune neuropathies and more recently, IgG antibodies in one with Graves' disease (Adler et al., Autoimmunity 18, 149-152, 1994) [1]. In the latter case, we were unable to find any relation between the occurrence of antibodies and thyroid disease. Now we report a detailed study on the anti-glycolipid antibodies in this patient. We found that her serum contained not only IgG but also a high level of anti-FucGM1 IgM antibodies, with a titer stable over a period of 5 years of treatment and follow-up. The carbohydrate structure of the epitope recognized by IgG and some of IgM antibodies seems to consist of Fuc-Gal-GalNAc-Gal- or a part of this sequence. Moreover, this patient's serum contained other IgM antibodies active against FucGM1 and also asialo GM1 glycolipids. Our results indicate that anti-FucGM1 ganglioside antibodies of G and M classes occur in serum of this patient with no apparent adverse health effects.

Topics: Antibody Specificity; Autoantibodies; Carbohydrate Sequence; Cross Reactions; Female; G(M1) Ganglioside; Graves Disease; Humans; Immunoglobulin G; Immunoglobulin M; Middle Aged; Molecular Sequence Data; Nervous System Diseases; Neutralization Tests

Concentrations of the four major brain gangliosides, GM1, GD1a, GD1b and GT1b, biochemical markers of neuronal membranes, were determined in the cerebrospinal fluid (CSF) of 20 children with autism and in 25 controls. In addition, the gangliosides were determined in children with different forms of non-progressive neurological disorders lacking clinical features of autism. GM1, GD1a, GD1b and GT1b were significantly increased in patients with autism compared with age-matched controls and children with non-progressive neurological disorders. The gangliosides have previously been shown to have a function in synaptic transmission and increased synaptic activity leads to added release of gangliosides. Our finding of increased CSF levels of gangliosides in autism suggests increased synaptic activity in this disorder.

Topics: Adolescent; Age Factors; Autistic Disorder; Child; Child, Preschool; Chromatography, Thin Layer; Data Interpretation, Statistical; G(M1) Ganglioside; Gangliosides; Humans; Intellectual Disability; Nervous System Diseases; Synapses; Synaptic Membranes; Synaptic Transmission

We reviewed the clinical and electrophysiologic features of 36 patients with increased titers of IgM anti-GM1 antibodies. Mildly elevated titers of up to 3,200 were not associated with any particular clinical syndrome or disease. Clinically, 14 of 16 patients with highly elevated titers of 6,400 or higher had progressive weakness with lower motor neuron signs; six had active tendon reflexes and eight had absent reflexes, but none had definite upper motor neuron signs. Electrophysiologic studies showed spontaneous activity in all 14 patients, one or more motor conduction blocks in nine, slowed motor conductions in one, and normal conductions in four patients. None had abnormal sensory conductions. These patients presented with a syndrome that has features of, but is distinct from, both motor neuron disease and demyelinating neuropathy.

Topics: Adult; Aged; Antibodies; Electrophysiology; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Male; Middle Aged; Motor Activity; Motor Neuron Disease; Nervous System Diseases; Neural Conduction; Paraproteinemias; Reflex, Stretch

We review clinical, neurophysiological, immunological, and experimental data concerning multifocal motor neuropathy (MMN), a newly recognized disorder that mimics MND. It is separated from MND by the presence of multifocal conduction block (CB) demonstrated electrophysiologically, and in some instances by the association of high titers of GM1 antibodies. The possible immunopathogenetic effect of GM1 antibodies is discussed. However, 70% of patients with MMNCB do not have elevated titers of GM1 antibodies, but may respond nevertheless to immunosuppressive treatment. Thus, so far unrecognized antibodies may react against some other epitopes in the paranodal region than those attacked by GM1 antibodies to cause CB.

Topics: Animals; Antibodies; Antibodies, Anti-Idiotypic; Demyelinating Diseases; G(M1) Ganglioside; Humans; Immunoglobulin M; Mice; Motor Neuron Disease; Nervous System Diseases; Neural Conduction; Rabbits; Rats

Several gangliosides of human nervous tissues have been reported to be potential target antigens in autoimmune neuropathies. To explain the diversity of clinical symptoms in patients with antiganglioside antibodies, we have searched for ganglioside antigens that are specific to individual nervous tissues such as motoneurons, peripheral motor nerves, and sensory nerves. Although the major ganglioside compositions were not different among human peripheral motor and sensory nerves, fucosyl-GM1 was found to be expressed in sensory nervous tissue but not in spinal cord, motor nerve, and sympathetic ganglia. Sera from several patients with sensory nerve involvement also reacted with fucosyl-GM1 as well as GM1. Thus, fucosyl-GM1 may be a responsible target antigen for developing sensory symptoms in some patients with autoimmune neuropathies.

Topics: Animals; Autoantigens; Autoimmune Diseases; G(M1) Ganglioside; Humans; Nervous System Diseases; PC12 Cells; Peripheral Nerves; Rats; Sense Organs

Clinical and experimental findings suggest that humoral factors, such as anti-peripheral nerve antibodies and cytokines, may be implicated in the immunopathogenesis of Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Interleukin-6 (IL-6) is a multifunctional cytokine that promotes immunoglobulin synthesis by B lymphocytes. Increased IL-6 release is associated with autoantibody production in a number of immune-mediated and neoplastic disorders. To investigate the possible involvement of abnormal IL-6 release in inflammatory polyneuropathies, we assayed IL-6 levels in the cerebrospinal fluid (CSF) and serum of 23 patients with acute GBS and seven with CIDP. We also studied 69 patients with other non-inflammatory neurological diseases (NIND), 25 with other inflammatory neurological diseases (IND), four with brain tumors (BT), and 15 normal donors (serum alone) as controls. We found detectable levels of IL-6 in the CSF of 57% of GBS, 43% of CIDP, 60% of IND, 75% of BT, and 4% of NIND. In GBS patients, no correlation was found between CSF IL-6 values and other laboratory or clinical parameters, such as CSF total protein, CSF albumin, CSF IgG, CSF/serum albumin ratio, functional disability score, and time elapsed from disease onset. Serum IL-6 levels were increased in six of 23 (26%) GBS, in one of 39 (3%) NIND, and in one of seven (14%) IND, but in none of the CIDP or BT patients. There was no correlation between serum and CSF IL-6 values, but cytokine levels in GBS sera correlated with time elapsed from clinical onset.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acute Disease; Adolescent; Adult; Aged; Aged, 80 and over; Autoantibodies; Chronic Disease; Demyelinating Diseases; Enzyme-Linked Immunosorbent Assay; Female; G(M1) Ganglioside; Humans; Immunoglobulin G; Immunoglobulin M; Interleukin-6; Male; Middle Aged; Nervous System Diseases; Polyradiculoneuropathy

The semisynthetic ganglioside derivative LIGA20 (II3Neu5-AcGgOse4-2-d-erythro-1,3-dihydroxy-2-dichloro-ac eta mide-4-trans-octadacene) was found to be about ten times more potent than the natural ganglioside GM1 in protecting neurones in culture against glutamate toxicity. Here we show that, in vivo, LIGA20 attenuated toxicity of the glutamate receptor agonist N-methyl-D-aspartate (NMDA). In seven-day-old rats NMDA was injected intracerebroventricularly, while LIGA20 or GM1 were administered subcutaneously. The loss in brain weight, five days following treatment, was used to estimate NMDA toxicity. Significant protection was observed with 2.5 mg kg-1 of LIGA20, while at least ten times this dose was needed for GM1, thus suggesting the superior in vivo pharmacological action of LIGA20.

Topics: Animals; Animals, Newborn; G(M1) Ganglioside; Injections, Intraventricular; N-Methylaspartate; Nervous System Diseases; Organ Size; Rats; Sphingosine

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

Antibodies to GM1 or Gal(beta 1-3)GalNAc are associated with motor or sensorimotor neuropathy and with motor neuron disease. To investigate the role of these antibodies in the neurological disorder, rabbits were immunized with GM1 or with Gal(beta 1-3)GalNAc-BSA, and studied serologically, electrophysiologically and pathologically. Development of antibodies to the immunizing antigens was associated with a fall in the ratio of the amplitudes of the compound muscle action potential evoked by proximal versus distal stimulation of the sciatic nerve. Pathological studies revealed mild axonal degeneration and immunoglobulin deposits at the nodes of Ranvier in peripheral nerve, resembling those reported in a patient with motor neuropathy, motor conduction block and anti-GM1 antibodies. These studies provide evidence that anti-GM1 or anti-Gal(beta 1-3)GalNAc antibodies cause conduction abnormalities and indicate that the antibodies may exert their effect, in part, by binding at the nodes of Ranvier in peripheral nerve.

Topics: Animals; Antibodies; Antibody Formation; Autoimmune Diseases; Electrophysiology; Fluorescent Antibody Technique; G(M1) Ganglioside; Immunoglobulins; Nervous System Diseases; Rabbits; Ranvier's Nodes

Sera from 54 patients with Guillain-Barré syndrome (GBS), 34 patients with other neurological diseases (OND) and 32 healthy controls were tested for antibodies to total lipid fractions and higher neutral glycolipid fractions isolated from human and dog nerves, purified Forssman glycolipid and a panel of purified neutral glycolipids by both an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-overlay technique. IgM and IgG antibodies to total lipid fractions, as well as to galactocerebroside, ceramide dihexoside, ceramide trihexoside, and globoside were not significantly elevated in the sera of GBS patients as compared to controls. High levels of anti-asialo-GM1 IgG antibodies, however, were detected in 6 of 54 (11%) GBS patients and 1 of 30 (3%) OND patients. Intense reactivity with purified Forssman glycolipid and a number of glycolipid antigens in higher neutral glycolipid enriched fractions of human cauda equina and dog sciatic nerves was noted by TLC-immunostaining in many GBS and control sera. Although the levels of anti-Forssman IgM were significantly decreased in GBS sera compared with normal sera (P less than 0.05) and OND sera (P less than 0.02), the levels of anti-Forssman IgG antibodies were not significantly different. With the possible exception of IgG antibodies to asialo-GM1, our results suggest that serum antibodies against Forssman glycolipid and neutral glycolipids are not significantly elevated in GBS patients and, thus, are unlikely to play an important role in the pathogenesis of this disease.

Topics: Animals; Autoantibodies; Carbohydrate Sequence; Dogs; Enzyme-Linked Immunosorbent Assay; Forssman Antigen; G(M1) Ganglioside; Glycolipids; Glycosphingolipids; Humans; Immunoglobulin G; Immunoglobulin M; Molecular Sequence Data; Nervous System Diseases; Polyradiculoneuropathy

Topics: Animals; Behavior, Animal; Brain Ischemia; G(M1) Ganglioside; Male; Nervous System Diseases; Rats; Rats, Inbred Strains; Time Factors

After 7 days of treatment with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), 30 mg/kg i.p., tyrosine hydroxylase (TH) and aromatic L-amino acid decarboxylase (AAAD) activities are decreased by more than 50% in the mouse striatum. Within 30 days, AAAD activity returns while TH activity remains depressed. TH activity can be restored to near normal by chronic treatment with GM1 ganglioside, 30 mg/kg i.p.

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Animals; Aromatic Amino Acid Decarboxylase Inhibitors; Behavior, Animal; Chromatography, High Pressure Liquid; Corpus Striatum; Dopamine; G(M1) Ganglioside; Male; Mice; MPTP Poisoning; Nervous System Diseases; Tyrosine 3-Monooxygenase

We compared anti-GM1 IgM antibody titers in patients with various neurologic diseases and in normal subjects. We found increased titers in patients with lower motor neuron disease, sensorimotor neuropathy, or motor neuropathy with or without multifocal conduction block. In patients with other diseases, titers are similar to those in normal individuals, suggesting that anti-GM1 antibody levels are not increased nonspecifically after neural injury or inflammatory diseases. Anti-GM1 antibodies in many of the patients occur as monoclonal gammopathies, predominantly of lambda light-chain type, but the antibodies are sometimes polyclonal with normal or increased serum IgM concentrations. Most of the anti-GM1 antibodies appear to react with the Gal(beta 1-3)GalNAc epitope which is shared with asialo-GM1 and GD1b, but in some patients the antibodies are more specific for GM1 and associated with motor neuropathy. Patients with motor or sensorimotor peripheral neuropathy or lower motor neuron disease should be tested for anti-GM1 antibodies or anti-Gal(beta 1-3)GalNAc antibodies, as therapeutic reduction in antibody concentrations was reported to result in clinical improvement in some patients.

Topics: Adult; Aged; Autoantibodies; Central Nervous System Diseases; Female; G(M1) Ganglioside; Humans; Immunoglobulin M; Male; Middle Aged; Motor Neurons; Nervous System Diseases; Neuromuscular Diseases; Peripheral Nervous System Diseases; Sensation; Syndrome

Cultures of chicken day 8 embryo retinal cells, essentially free of contaminating non-neuronal elements, were used to examine the neurotoxicity of various excitatory amino acid transmitter receptor agonists. At 7 days in vitro, N-methyl-D-aspartate (NMDA), following 24 hr exposure to 0.1-1.0 mM, destroyed 60-70% of the multipolar neurons, but apparently spared photoreceptors. The cytotoxic effect of NMDA was prevented by extracellular Mg2+ or phencyclidine, suggesting a role for the NMDA ion channel; competitive NMDA antagonists were also neuroprotective. The mixed excitatory amino acid receptor agonist glutamate (0.1-1.0 mM) was also neurotoxic (approximately 70% loss of multipolar neurons) and strongly blocked by NMDA (but weakly by non-NMDA) antagonists and Mg2+, indicating a major action at NMDA receptors. As with NMDA, glutamate did not appear to affect photoreceptors. The neurotoxic action of kainate against multipolar retinal neurons, as reported by others, was confirmed here. Kainate neuronal injury was sensitive to the quinoxalinedione non-NMDA antagonists 6,7-dinitroquinoxaline-2,3-dione (DNQX) and 6-cyanoquinoxaline-2,3-dione (CNQX), but not to Mg2+ or phencyclidine. Ibotenate and quisqualate, even at millimolar concentrations, were not neurotoxic. The monosialoganglioside GM1 was also effective in reducing NMDA and non-NMDA agonist neurotoxicity to retinal neurons. Maximal ganglioside benefit required 1-2 hr of pretreatment with 100-200 microM GM1. The percentage of multipolar neurons remaining after the neurotoxin insult approximately doubled with GM1 treatment. Gangliosides may thus have a therapeutic potential in excitatory amino acid-initiated neuropathologies.

Topics: Amino Acids; Animals; Cattle; Cell Survival; Cells, Cultured; Chick Embryo; G(M1) Ganglioside; Glutamates; Kainic Acid; Nervous System Diseases; Neurons; Receptors, Cell Surface; Receptors, N-Methyl-D-Aspartate; Retina

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

Gangliosides are thought to have a role in neuronal development and regeneration while anti-ganglioside antibodies have been shown to impair these processes. In the present work we examined whether the neuronal degeneration in Alzheimer's disease is associated with the presence of anti-ganglioside antibodies. A significant level of antibodies specific to ganglioside GM1 but not to other gangliosides (GD1a, GD1b, GT1b and GQ1b) was found in patients with Alzheimer's disease as compared to normal age matched controls. A high level of antibodies to GM1 was also found in patients with multi-infarct dementia and Parkinson's disease with dementia but not in non-demented patients with other neurodegenerative diseases. These results may reflect a specific change in ganglioside metabolism which is associated with the neurodegenerative processes underlying Alzheimer's disease and other causes of dementia.

Topics: Adult; Aged; Aged, 80 and over; Alzheimer Disease; Autoantibodies; Female; G(M1) Ganglioside; Humans; Male; Middle Aged; Nervous System Diseases

A high incidence of antibody to asialo GM1 was observed in the sera from the patients with Systemic Lupus Erythematosus (SLE) and Behçet's disease with neurological manifestations, using Enzyme Linked Immunosorbent Assay (ELISA), and Thin-layer Chromatography (TLC) immunostaining. The sera from 60 out of 102 cases of SLE with neurological disorders and 6 out of 10 patients with neuro Behçet's disease showed antibody activity against asialo GM1 but not against the asialo GM2, GM1 and galactocerebroside. In 7 out of 123 cases SLE having a history without neurological manifestations and 1 out of 19 Behçet's patients without neurological disorders, antiasialo GM1 antibody could be detectable. However, sera from the patients with other autoimmune diseases, such as RA (60 cases) and P S S (32 cases) or from normal subjects did not show any antibody activity against asialo GM1. Antiasialo GM1 antibody activity presents in both IgM and IgG immunoglobulin classes by class specific ELISA and TLC immunostaining. These studies suggest that detection of antiasialo GM1 antibody may be useful in clinical diagnosis and these autoantibody plays a important role in the pathogenesis of neurological manifestations accompanying SLE and Neuro-Behçet's disease.

Topics: Antigen-Antibody Complex; Behcet Syndrome; Chromatography, Thin Layer; Enzyme-Linked Immunosorbent Assay; G(M1) Ganglioside; Glycosphingolipids; Humans; Immunoglobulin G; Immunoglobulin M; Lupus Erythematosus, Systemic; Nervous System Diseases

An increasing focus on the mechanism of synaptic neurochemistry in pediatric neurology, may lead to a better understanding of the pathophysiology of many disorders and result in a more rational approach to their pharmacotherapy. With the burgeoning list of putative neurotransmitters in brain, and the growing evidence of co-localization of many of these neurotransmitters, chemical neurotransmission likely involves a higher degree of complexity than appreciated heretofore. The potential role of neurotransmitter dysfunction in the pathophysiology of neurologic and behavior disorders of children, should not be considered as restricted to those disorders that involve selective neuronal loss, but may encompass a much wider spectrum of syndromes due to metabolic abnormalities, as well as disturbances of the finer features of chemical neurotransmission.

Topics: Afferent Pathways; Animals; Brain Damage, Chronic; Cats; Central Nervous System; Cerebral Cortex; Chemical Phenomena; Chemistry; Child; Child, Preschool; G(M1) Ganglioside; gamma-Aminobutyric Acid; Gangliosidoses; Humans; Mental Disorders; Methylazoxymethanol Acetate; Nerve Tissue; Nervous System Diseases; Neurons; Neurotransmitter Agents; Rats; Sympathetic Nervous System; Synapses; Tourette Syndrome

The effect of exogenous GM1 ganglioside on selective neurotoxin-induced lesions of serotonin (5-HT) and noradrenaline (NA) neurons in both the central and peripheral nervous systems has been investigated in developing and adult rats and mice by employing neuro- and histochemical techniques. 5,7-Dihydroxytryptamine (5,7-HT) was used to lesion 5-HT neurons, and 6-hydroxydopamine (6-OH-DA) was used to lesion NA neurons. In most lesion models investigated the neurotoxin causes primarily an axonal nerve terminal damage without notably affecting the perikarya. There was no evidence indicating that GM1 interferes with the primary and direct neurodegenerative actions of 5,7-HT or 6-OH-DA on 5-HT and NA nerve terminals, respectively. In all lesion models GM1 had in the chronic stage a counteracting effect on the neurotoxin-induced nerve terminal lesion or enhanced regrowth. The present results are compatible with the view that GM1 has a regrowth-stimulating effect and/or protective actions against secondary retrograde degeneration following the initial nerve terminal lesion induced by the neurotoxin.

Topics: 5,7-Dihydroxytryptamine; Animals; Animals, Newborn; Female; G(M1) Ganglioside; Gangliosides; Hydroxydopamines; Male; Nervous System Diseases; Norepinephrine; Oxidopamine; Rats; Rats, Inbred Strains; Serotonin; Sympathectomy, Chemical

Topics: Animals; Autoantibodies; Autoimmune Diseases; Brain Neoplasms; Cell Line; Cytotoxicity Tests, Immunologic; G(M1) Ganglioside; Glycosphingolipids; Guinea Pigs; Humans; Lupus Erythematosus, Systemic; Mice; Nervous System Diseases; Rabbits

A radioassay for the rapid determination of GM1 ganglioside concentration in small volumes of CSF from individual patients is described. The assay utilizes the high-affinity interaction between cholera enterotoxin and GM1 ganglioside. The lower detection limit of GM1 ganglioside by this radioassay under the described incubation conditions is 2.5 ng/ml. The radioassay-determined lumbar CSF GM1 ganglioside concentrations in a small group of patients with diverse neurologic disorders are presented. The radioassay GM1 ganglioside concentration is in good agreement with the GM1 ganglioside concentration determined, in one patient, by the tlc-densitometry technique.

Topics: Colorimetry; G(M1) Ganglioside; Gangliosides; Humans; Iodine Radioisotopes; Nervous System Diseases; Radioisotope Dilution Technique