Expression of GD3 ganglioside by developing rat cerebellar Purkinje cells in situ

GD3 is a major ganglioside of the immature vertebrate CNS, and its expression is suggested to be characteristic of immature neuroectodermal cells. Using immunocytochemistry on cryostat sections of developing rat cerebellum with a monoclonal antibody specific for GD3, we have found that GD3 begins to be expressed on the plasma membrane of Purkinje cell bodies and dendrites beginning at postnatal day 7. Staining became brighter as the dendritic tree of the cells enlarged. As the Purkinje cells began to mature in different folia, they became GD3+, until by 15 days postnatal all Purkinje cells were GD3+. Positive staining of the dendritic tree was still present in the adult cerebellum. Using a monoclonal antibody 7-8D2, which recognizes cerebellar granule cells and their axons (the parallel fibres), and polyclonal antibodies against a synaptic vesicle component synaptophysin, double-immunofluorescence staining together with anti-GD3 antibodies suggested that the appearance of GD3 immunoreactivity did not correlate either with the ingrowth of parallel fibres or the presence of their synapses on Purkinje cell dendrites. However, comparison with earlier morphological studies showed that the appearance of GD3 immunoreactivity correlated well with the formation of climbing fibre synapses on Purkinje cell dendrites and the onset of the rapid expansion of the dendritic tree. These results are in keeping with the idea that elevated GD3 concentrations are found in certain cell types during periods of rapid growth or high metabolic activity but also show that this is not only restricted to immature cells.     

Spectrum of neurological diseases associated with antibodies to minor gangliosides GM1b and GalNAc-GD1a

The authors reported the neurological disease spectrum associated with autoantibodies against minor gangliosides GM1b and GalNAc-GD1a. IgG and IgM antibody reactivity against gangliosides GM1, GM2, GM1b, GD1a, GalNAc-GD1a and GQ1b was investigated in sera from 7000 consecutive patients who had various neurological conditions. The clinical diagnoses for 456 anti-GM1b-positive patients were Guillain-Barré syndrome (GBS, 71%), atypical GBS with preserved deep tendon reflexes (12%), Fisher syndrome (10%), Bickerstaff's brainstem encephalitis (2%), ataxic GBS (2%) and acute ophthalmoparesis (1%). For 193 anti-GalNAc-GD1a-positive patients, the diagnoses were GBS (70%), atypical GBS (16%), Fisher syndrome (10%) and Bickerstaff's brainstem encephalitis (3%). Of the patients with GBS or atypical GBS, 28% of 381 anti-GM1b-positive and 31% of 166 anti-GalNAc-GD1a-positive patients had neither anti-GM1 nor anti-GD1a antibodies. Of those patients with Fisher syndrome, Bickerstaff's brainstem encephalitis, ataxic GBS or acute ophthalmoparesis, 33% of 67 anti-GM1b-positive, and 52% of 25 anti-GalNAc-GD1a-positive patients had no anti-GQ1b antibodies. Autoantibodies against GM1b and GalNAc-GD1a are associated with GBS, Fisher syndrome and related conditions. These antibodies should provide useful serological markers for identifying patients who have atypical GBS with preserved deep tendon reflexes, ataxic GBS, Bickerstaff's brainstem encephalitis or acute ophthalmoparesis, especially for those who have no antibodies to GM1, GD1a or GQ1b. A method to prepare GM1b was developed.     

Cerebellar ataxia and acute motor axonal neuropathy associated with Anti GD1b and Anti GM1 antibodies.

The anti-GD1b antibody is known to bind to the cerebellar granular layer or spinocerebellar Ia fibers. A few cases of anti-GD1b positive acute inflammatory demyelinating polyneuropathy with prominent cerebellar ataxia were reported. Recently, we encountered a middle-aged woman with Guillain Barré syndrome (GBS) with severe cerebellar ataxia and relatively mild motor weakness. Anti-GD1b Ig G antibody and anti-GM1 Ig G antibody titers were markedly elevated in her serum. She was diagnosed with acute motor axonal neuropathy (AMAN) with prominent cerebellar ataxia based on the results of the serial nerve conduction study suggesting axonal neuropathy. This case presents the clinico-pathogenic role of autoantibodies to the GD1b and the GM1 in acute inflammatory neuropathy.     

Reactivity of a human monoclonal anti-GM1 and anti-GD1b IgM antibody with human neurons in cultures

A serum containing a monoclonal IgM λ with anti-GM1 and anti-GD1b activity was obtained from a patient with upper motor neuron syndrome. By indirect immunocytochemical techniques with double staining, the patient's IgM strongly stained membranes of neurons in primary cultures of fetal central and peripheral nervous system. It was cytotoxic for neurons in two human neuroblastoma established cell lines in a complement-dependent chromium release assay. These results are in keeping with the hypothesis of a direct pathogenetic role of such monoclonal anti-GM1 and GD1b IgM antibodies.     

Dysfunction of nodes of Ranvier: a mechanism for anti-ganglioside antibody-mediated neuropathies

Autoantibodies against gangliosides GM1 or GD1a are associated with acute motor axonal neuropathy (AMAN) and acute motor-sensory axonal neuropathy (AMSAN), whereas antibodies to GD1b ganglioside are detected in acute sensory ataxic neuropathy (ASAN). These neuropathies have been proposed to be closely related and comprise a continuous spectrum, although the underlying mechanisms, especially for sensory nerve involvement, are still unclear. Antibodies to GM1 and GD1a have been proposed to disrupt the nodes of Ranvier in motor nerves via complement pathway. We hypothesized that the disruption of nodes of Ranvier is a common mechanism whereby various anti-ganglioside antibodies found in these neuropathies lead to nervous system dysfunction. Here, we show that the IgG monoclonal anti-GD1a/GT1b antibody injected into rat sciatic nerves caused deposition of IgG and complement products on the nodal axolemma and disrupted clusters of nodal and paranodal molecules predominantly in motor nerves, and induced early reversible motor nerve conduction block. Injection of IgG monoclonal anti-GD1b antibody induced nodal disruption predominantly in sensory nerves. In an ASAN rabbit model associated with IgG anti-GD1b antibodies, complement-mediated nodal disruption was observed predominantly in sensory nerves. In an AMAN rabbit model associated with IgG anti-GM1 antibodies, complement attack of nodes was found primarily in motor nerves, but occasionally in sensory nerves as well. Periaxonal macrophages and axonal degeneration were observed in dorsal roots from ASAN rabbits and AMAN rabbits. Thus, nodal disruption may be a common mechanism in immune-mediated neuropathies associated with autoantibodies to gangliosides GM1, GD1a, or GD1b, providing an explanation for the continuous spectrum of AMAN, AMSAN, and ASAN.     

Temporal profile of anti-ganglioside antibodies and their relation to clinical parameters and treatment in Guillain-Barré syndrome

Elevated anti-ganglioside antibody levels mainly of anti-GM1 and anti-GD1a specificities have been reported in THE serum of patients with Guillain–Barré syndrome (GBS). The relevance of anti-ganglioside antibodies other than anti-GM1 and anti-GD1a IgG antibodies and the temporal profile of anti-ganglioside antibodies in GBS is less clear. We studied serum antibodies to GM1, GD1a, GD1b, GQ1b, sulfatide and cardiolipin of the IgM, IgG and IgA classes over the course of GBS in patients who were untreated or treated with highdose intravenous immunoglobulin (IvIg). Antibodies to GD1b, GQ1b, sulfatide and cardiolipin were not detected in the sera of the GBS patients examined in this study. Anti-GM1 IgG titers peaked around 40 days and anti-GD1a IgM around 90 days after GBS onset. Titers of anti-GM1 IgG antibodies decreased following IvIg treatment. Patients with antibody peaks, defined as fivefold or higher increase in antibody titer compared to the lowest antibody titer over the course of GBS, had higher disability scores during the first two weeks of GBS and a worse clinical outcome (anti-GM1 IgG and anti-GD1a IgM antibody peaks) and axonal damage (anti-GD1a IgM antibody peaks), compared to patients without peak antibody titers. Anti-GM1 IgG and anti-GD1a IgM antibodies are thus strongly associated with more severe- and predominantly axonal cases of GBS. The appearance of anti-GM1 IgG and anti-GD1a antibody peaks in the serum after the termination of the acute phase of GBS suggests that these antibodies are produced secondary to nerve damage in GBS. The data does not exclude the possibility that secondarily secreted anti-GM1 IgG and anti-GD1a IgM antibodies may themselves be biologically active and play a role in disease propagation and/or recovery from disease in some patients with GBS.     

Range of cross reactivity of anti-GM1 IgG antibody in Guillain-Barré syndrome

The cross reactivity of anti-GM1 IgG antibody with various gangliosides and asialo-GM1 in serum samples from 27 patients with Guillain-Barré syndrome was investigated. An enzyme linked immunosorbent assay (ELISA) absorption study showed that anti-GM1 IgG antibody cross reacted with asialo-GM1 in 52% of the patients, GM1b in 41%, GD1b in 22%, and GalNAc-GD1a in 19%, and that it did not cross react with GM2, GT1b, or GQ1b. The antibody that cross reacted with GD1b was associated with a high frequency of cranial nerve involvement and negative Campylobacter jejuni serology. Anti-GM1 IgG antibody has a broad range of cross reactivity which may contribute to various clinical variations of Guillain-Barré syndrome.     

Antibodies to GD1alpha and to GQ1beta in Guillain-Barré syndrome and the related disorders.

Certain species of anti-ganglioside antibodies are associated with specific clinical features in various neurologic diseases. Serum autoantibodies to these minor gangliosides were investigated in a number of neurological diseases in order to examine the biological functions of GD1alpha and GQ1beta. Eleven patients with Guillain-Barré syndrome had remarkably high IgG anti-GD1alpha antibody titers, but no GD1alpha was detected in human peripheral nerve. An absorption study showed that IgG anti-GD1alpha antibodies from eight of the 11 patients were significantly absorbed by GD1a and GM1b, indicative that the IgG anti-GD1alpha antibodies cross-react with GD1a and GM1b. Both GD1a and GM1b have been reported to be target molecules for serum antibodies in certain patients with Guillain-Barré syndrome. GD1alpha may induce the production of IgG anti-GD1alpha antibody which cross-reacts with GD1a or GM1b, and subsequently functions in the development of Guillain-Barré syndrome. The IgGs from six patients with Fisher's syndrome who had the anti-GQ1beta antibody had anti-GQ1b activity as well. All the patients had external ophthalmoplegia, but no GQ1beta was detected in the human oculomotor nerve, further evidence that GQ1b, not GQ1beta, is the molecule targeted by the autoantibody in Fisher's syndrome.     

Antibodies to the ganglioside GD1b in a patient with motor neuron disease and thyroid adenoma

Patients with motor neuron disease with thyroid disorders have been described, although the relationship between the two conditions is unclear. We treated a patient with amyotrophic lateral sclerosis who also had a follicular adenoma of the thyroid gland. Because thyroid gland plasma membranes contain high concentrations of complex gangliosides, such as GD1b, and some patients with motor neuron disease have IgM antibodies to GD1b, we decided to assay serum from this patient for the presence of antiganglioside antibodies. IgM antibodies to GD1b were detectable at serum dilutions of 1:500 and 1:1000 by enzyme-linked immunosorbent assay. While these titers are less than those usually described in patients with plasma cell dyscrasia, they are well in excess of normal values. Antibody to GM1 was also detectable at a lower (1:100) dilution. We do not know the importance of the anti-GD1b antibodies in this patient, but it is possible that antibodies to GD1b are involved in this and other cases of motor neuron disease associated with thyroid disease.     

Antibodies to GM1(NeuGc) in Guillain-Barré syndrome after ganglioside therapy

N-Glycolylneuraminic acid-containing GM1 [GM1(Gc)] is a molecule for serum antibodies in patients with Guillain-Barré syndrome (GBS). To clarify the pathogenesis of GBS after treatment with bovine brain ganglioside, we investigated the presence of anti-GM1(Gc) antibody in patients who developed GBS after ganglioside injection. Serum samples were taken from nine Italian patients with GBS after ganglioside therapy as well as from untreated Italian (n=30) and Japanese (n=131) GBS patients. Bovine brain gangliosides fractionated in a column were used as antigens, and binding of serum IgG or IgM was examined. An absorption study of IgG anti-GM1(Gc) antibody was made with GM1, asialo-GM1, GM2, GD1a, and GD1b. Four of the nine patients who developed GBS after being administered gangliosides had IgG anti-GM1(Gc) antibodies. Anti-GM1(Gc) IgG antibody frequencies were higher in patients with GBS after ganglioside therapy than in those who were untreated. Rates of absorption of IgG anti-GM1(Gc) antibodies by GM1 were significantly higher (except for asialo-GM1 and GD1b) than by GM2 and GD1a. The presence of GM1(Gc) was confirmed in bovine brain immunochemically using cholera toxin and Hanganutziu-Deicher antibody. Secondary ion mass spectra showed that the structure of the ganglioside was consistent with that of GM1(Gc). GM1(Gc) was recognized more frequently in sera from patients who developed GBS after ganglioside therapy than in sera from untreated GBS patients. Because N-glycolylneuraminic acid-containing gangliosides seem to be highly immunogenic in humans, GM1(Gc) may act as an immunogen in some patients who develop GBS following ganglioside therapy.     

Binding of antibodies against GM1 and GD1b in human peripheral nerve

Human dorsal root ganglia (DRG), and ventral and dorsal roots were immunostained with rabbit antibodies recognizing GM1, GD1b, or both. Sera from rabbits immunized with GM1 or GD1b were separated in affinity columns into three fractions: Rab1, Rab2, and Rab3. Rab1 recognized only GM1, and Rab2 only GD1b; whereas Rab3 recognized both GM1 and GD1b, presumably by binding to the terminal galactosylβ1-3N-acetylgalactosaminyl residue. Rab2 and Rab3 immunostained most of the nerve cell bodies in the DRG and paranodal myelin of the ventral and dorsal roots, whereas Rab1 produced no significant immunostaining. These results show that GD1b is localized on the DRG neurons and the paranodal myelin of human peripheral nerve. These places may be the binding sites for anti-GD1b antibodies, including those cross-reactive with GM1, in the sera from patients with autoimmune neuropathies. GM1 may be dispersed in human DRG and dorsal and ventral roots. © 1997 John Wiley & Sons, Inc. Muscle Nerve 20: 840–845, 1997     

ANTIBODIES TO GM1(NEUGC) IN GUILLAIN-BARRE SYNDROME AFTER GANGLIOSIDE THERAPY

N-Glycolyneuraminic acid-containing GM1 [GM1(Gc)] is a molecule for serum antibodies in patients with Guillain-Barre syndrome (GBS). To clarify the pathogenesis of GBS after treatment with bovine brain ganglioside, we investigated the presence of anti-GM 1(Gc) antibody in patients who developed GBS after ganglioside injection. Serum samples were taken from nine Italian patients with GBS after ganglioside therapy as well as from untreated Italian (n = 30) and Japanese (n = 131) GBS patients. Bovine brain gangliosides fractionated in a column were used as antigens, and binding of serum IgG or IgM was examined. An absorption study of IgG anti-GM1(Gc) antibody was made with CMI, asialo-GM1, GM2, CD1a, and GD1b. Four of the nine patients who developed GBS after being administered gangliosides had IgG anti-GM1(Gc) antibodies. Anti-GM1(Gc) IgG antibody frequencies were higher in patients with GBS after ganglioside therapy than in those who were untreated. Rates of absorption of IgG anti-GM1(Gc) antibodies by GM1 were significantly higher (except for asialo-GM1 and GD1b) than by GM2 and GD1a. The presence of GM 1(Gc) was confirmed in bovine brain immunochemically using cholera toxin and Hanganutziu-Deicher antibody. Secondary ion mass spectra showed that the structure of the ganglioside was consistent with that of GM1(Gc). GM1(Gc) was recognized more frequently in sera from patients who developed GBS after ganglioside therapy than in sera from untreated GBS patients. Because N-glycolylneuraminic acid-containing gangliosides seem to be highly immunogenic in humans, GM1(Gc) may act as an immunogen in some patients who develop GBS following ganglioside therapy.     

Sensory neuropathy associated with monoclonal immunoglobulin M to GD1b ganglioside

A 67-year-old woman with a sensory polyneuropathy was shown to have a serum monoclonal immunoglobulin M λ antibody with a titer of 1:10,000 toward GD1b ganglioside. The immunoglobulin M also reacted with some other gangliosides containing disialosyl groups such as GD2, GD3, and GQ1b, but it did not react with GM1, LM1, or GD1a. The principal reactive ganglioside in human cauda equina was GD1b.     

Motor neuron syndrome and monoclonal IgM with antibody activity against gangliosides GM1 and GD1b

We demonstrated that an IgM M-protein from a patient with motor neuron syndrome had antibody activity against gangliosides GM1, GD1b, and asialo GM1. Studies with a sugar-binding lectin suggested that the epitope in the patient's M-IgM involved the Gal(beta 1-3) GalNAc moiety. Immunohistological techniques demonstrated staining of axons in the lumbar roots, granular cells, and white matter in the cerebellum by the patient's M-IgM. We propose that, in this case, an autoimmune mechanism of motor neuron syndrome associated with a monoclonal protein is most likely.     

Anti-glycolipid antibodies in the diagnosis of autoimmune neuropathies

Recent years have seen major progress in our understanding of the clinical pathophysiology of autoimmune neuropathies particularly with the identification and analysis of antibodies to gangliosides and related glycolipids in the serum of patients. Anti-glycolipid antibodies react with epitopes on the carbohydrate region of glycolipid molecules and can be routinely measured by standard immunoassays. In multifocal motor neuropathy, IgM anti-GM1 antibodies that cross react with GD1b and asialo-GM1 are detectable in around 50p. 100 of cases. This condition may clinically resemble certain forms of lower motor neurone disease. IgM anti-GD1b antibodies are found in IgM paraproteinaemic neuropathy characterised by profound sensory ataxia. In the anti-myelin associated glycoprotein (anti-MAG) IgM paraproteinaemic neuropathy, antibodies also react with the acidic glycolipids, sulphated glucuronyl paragloboside and its higher lactosaminyl homologue (SGPG and SGPLG). Thus a variety of chronic syndromes can be defined by their anti-glycolipid antibody profile. In Guillain-Barré syndrome, anti-GM1, GM1b, GD1a and GalNAc-GD1a antibodies are found in patients with acute motor axonal neuropathy (AMAN) and anti-GQ1b IgG antibodies are a very sensitive and specific marker for the Miller Fisher syndrome. Many other anti-glycolipid antibodies are being increasingly identified in other neuropathy subtypes. The article will summarise existing clinical and serological information in this field.     

Sensorimotor demyelinating neuropathy with IgM antibody against gangliosides GD1a, GT1b and GM3

We report a patient with sensorimotor demyelinating neuropathy with high-titer IgM antibody against gangliosides GD1a, GT1b and GM3. The patient was a 65-year-old male who was hospitalized with chief complaints of muscular weakness of all limbs and numbness of the hands and feet. Nerve-conduction studies revealed reduced conduction velocities of the motor nerves with increased temporal dispersion and loss of sensory nerve action potentials. Treatment with steroids was ineffective. IgM antibody against GD1a, GT1b and GM3, which are known to be the ligands for myelin-associated glycoprotein (MAG), might have played a role in the demyelination in this patient by inhibiting adhesion between myelin and axonal membrane.     

Anti-GM1 ganglioside antibodies with differing fine specificities in patients with multifocal motor neuropathy

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.     

An acute axonal form of Guillain-Barré syndrome with antibodies against gangliosides GM1 and GD1b--a case report

We reported a case of Guillain-Barré syndrome with autoantibodies against gangliosides GM1 and GD1b, which has not been reported yet. A 25-year-old man was admitted with a 7-day history of acute progressive weakness in the extremities. Two weeks before admission he had suffered from an episode of watery diarrhea. Neurological examination revealed areflexia and tetraparesis without any sensory impairment. Respiration and cranial nerves were not involved. The CSF protein level was 157 mg/dl with normal cellularity on the 14th illness day. The maximum M potential amplitude was 0.1 mV, which was 2% of the lower limit of normal, whereas motor and sensory nerve conduction velocities were normal on day 22. Repeated electrophysiological studies suggested that the predominant process was axonal degeneration. Although he received plasmapheresis at the acute phase, four months after onset he continued to have distal dominant limb weakness with wasting. High-performance thin-layer chromatography with immunostaining revealed that his serum IgG reacted with GM1, GD1b, and asialo-GM1. Enzyme-linked immunosorbent assay showed that anti-glycolipids antibodies titers decreased, concurrent with clinical course. Immunoabsorption study demonstrated that antibodies with anti-GM1 activity were absorbed with liposomes containing purified GD1b, indicating that autoantibodies bind to the galactosyl (beta 1-3) N-acetylgalactosaminyl moiety which is shared by GM1, GD1b, and asialo-GM1. There have been several reports of lower motor neuron diseases with monoclonal IgM antibody to GM1, GD1b, and asialo-GM1. This case suggested that the transient rise in these anti-carbohydrate antibodies may be involved in the pathogenesis of acute axonal degeneration of motor nerve as well as paraproteinemic motor neuron diseases.     

Antiganglioside antibody in patients with Guillain-Barré syndrome who show bulbar palsy as an initial symptom

OBJECTIVES: To identify valuable antiganglioside antibodies that support the diagnosis of Guillain-Barré syndrome (GBS) and its variants in patients showing bulbar palsy as an initial symptom. METHODS: Medical records of 602 patients with GBS or its variants were reviewed. Fifteen patients had bulbar palsy as an initial symptom. Serum antibodies against GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, and GQ1b were examined in 13 of them. RESULTS: Serum antiganglioside antibodies were positive in 11 (85%) patients. IgG anti-GT1a (n=8; 62%) and anti-GM1b (n=7; 54%) antibodies were often present, whereas all the patients had low or no anti-GM1 antibody activity. High anti-GD1a and anti-GQ1b IgG antibody titres were also present in some patients, but most had higher IgG antibody titres to GM1b or GT1a. All five patients with high IgG antibody titre to GM1b or GT1a only had had antecedent diarrhoea. Some patients with pharyngeal-cervical-brachial weakness (PCB) had IgG antibody to GT1a which did not cross react with GQ1b. Other patients with PCB had antibody to GT1a which cross reacted with GQ1b or antibody to GM1b, but anti-GM1b and anti-GT1a antibodies were not associated with the presence of bulbar palsy. All the patients who had no IgG antiganglioside antibodies recovered completely. CONCLUSIONS: Measurement of serum IgG anti-GT1a and anti-GM1b antibodies gives helpful support for the diagnosis of GBS and its variants when there is early involvement of the oropharyngeal function independently of other neurological findings which appear as the illness progresses.     

Patterns of serum IgM antibodies to GM1 and GD1a gangliosides in amyotrophic lateral sclerosis

We studied the incidence and clinical correlates of serum antibodies to GM1 and GD1a gangliosides in patients with classical amyotrophic lateral sclerosis (ALS) and other "motor nerve" syndromes. Serum antibodies to GM1 and GD1a gangliosides were measured using enzyme-linked immunosorbent assays. Our results showed that polyclonal immunoglobulin M (IgM) antibodies to the GM1 or GD1a ganglioside or both were present at serum dilutions of 1:25 to 1:4,000 in 78% (57/73) of patients with ALS. Only 8% of normal controls had similar antibodies. The pattern of serum antibody reactivity correlated with the pattern of clinical involvement in our patients. Selective reactivity to GD1a ganglioside was common when upper motor neuron signs were prominent. IgM reactivity to GM1 ganglioside was common in ALS patients with prominent lower motor neuron signs. Most patients with motor neuropathies had serum reactivity to both GM1 and GD1a gangliosides. These results provide further evidence of ongoing autoimmune processes in ALS patients. There is a strong relationship between serum antiganglioside antibodies and patterns of clinical involvement in ALS.