Detection of anti-ganglioside antibodies in Guillain-Barré syndrome and its variants by the agglutination assay

Sera from 40 patients with Guillain-Barré syndrome (GBS), including the subtypes acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and Miller Fisher syndrome (MFS) were examined for the presence of anti-ganglioside antibodies using the ganglioside agglutination assay, and the enzyme-linked immunosorbent assay (ELISA). In the ELISA system, sera were tested for IgM and IgG antibodies to GM1, GM2, GD1a, GD1b, GT1b, and GQ1b gangliosides. Antibodies to gangliosides were detected in 21 (53%) of the GBS patients by agglutination assay and in 17 (43%) of the patients by ELISA. Some of the sera reacted with more than one ganglioside. Antibodies were not found in the control sera that were studied. The agglutination assay may be useful for rapid screening of GBS sera for antibodies to multiple gangliosides.     

Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature

The objective of this study was to investigate if the clinical and electrophysiological phenotype of patients with polyneuropathy associated with IgM monoclonal gammopathy (IgM-PNP) is related to the presence of antibodies against gangliosides or myelin-associated glycoprotein (MAG). We compared clinical and nerve conduction study (NCS) characteristics of 11 IgM-PNP patients with antibodies against asialo-GM1 or gangliosides (GM1, GD1a, GD1b, GM2 or GQ1b) to 11 consecutive IgM-PNP patients with anti-MAG neuropathy and to 9 IgM-PNP patients without antibodies against either MAG or gangliosides. Patients with anti-ganglioside antibodies could not be differentiated from those with anti-MAG antibodies based on clinical characteristics. However, within the group of anti-ganglioside antibody positive patients, antibodies against GD1b and GQ1b were associated with a purely sensory neuropathy (p = 0.002), while asymmetric weakness with symmetric sensory loss was associated with anti-asialo-GM1 antibodies. In conclusion, polyneuropathy associated with IgM monoclonal gammopathy and anti-ganglioside antibodies clinically resembles anti-MAG neuropathy. Pure sensory neuropathy and marked asymmetry may suggest the presence of anti-ganglioside rather than anti-MAG antibodies.     

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.     

GQ1b-seronegative Fisher syndrome: clinical features and new serological markers

IgG anti-GQ1b antibodies are a powerful serological marker for the diagnosis of Fisher syndrome (FS), but little is known regarding serological markers in FS patients that do not have the autoantibodies. The authors analyzed IgG antibodies against gangliosides other than GQ1b, ganglioside complexes, and ganglioside-like lipo-oligosaccharide (LOS) of Campylobacter jejuni isolates from FS patients. We identified 24 (12%) patients with GQ1b-seronegative FS among 207 FS patients who had been referred to our laboratory for anti-ganglioside antibody testing. Patients with GQ1b-seronegative FS were male and had a history of antecedent gastrointestinal illness more frequently than FS patients with IgG anti-GQ1b antibodies. Other clinical features during the illness were not distinguishing for GQ1b-seronegative FS. Four (17%) of 24 patients with GQ1b-seronegative FS had IgG antibodies against single gangliosides such as GM1b, GD1a, or GT1a. Antibodies against GM1 and GT1a complex were detected in four GQ1b-seronegative FS patients, three of whom did not have antibodies against single gangliosides. Mass spectrometry analysis showed that C. jejuni isolates from FS patients had GD1c-, GalNAc-GM1b-, or GalNAc-GD1c-like LOS, and not GQ1b-like LOS, highlighting the utility of examining serum antibodies against these ganglioside mimics in GQ1b-seronegative FS patients. Seven (29%) had IgG antibodies against the LOS from C. jejuni strains expressing GD1c-, GalNAc-GM1b-, or GalNAc-GD1c-like LOS. These findings suggest that IgG antibodies against GM1b, GD1c, GalNAc-GM1b, and ganglioside complexes are serological markers for GQ1b-seronegative Fisher syndrome.     

Axonal Guillain-Barré syndrome: relation to anti-ganglioside antibodies and Campylobacter jejuni infection in Japan

To clarify the relations of the axonal form of Guillain-Barré syndrome (GBS) to anti-ganglioside antibodies and Campylobacter jejuni infection, 86 consecutive Japanese GBS patients were studied. Electrodiagnostic criteria showed acute inflammatory demyelinating polyneuropathy in 36% of the patients and acute motor axonal neuropathy (AMAN) in 38%. Frequent anti-ganglioside antibodies were of the IgG class and against GM1 (40%), GD1a (30%), GalNAc-GD1a (17%), and GD1b (21%). Identified infections were C. jejuni (23%), cytomegalovirus (10%), Mycoplasma pneumoniae (6%), and Epstein-Barr virus (3%). There was a strong association between AMAN and IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b. Almost all the patients with at least one of these antibodies had the AMAN pattern or rapid resolution of conduction slowing/block possibly because of early-reversible changes on the axolemma. C. jejuni infection was frequently associated with AMAN or anti-ganglioside antibodies, but more than half of the patients with AMAN or anti-ganglioside antibodies were C. jejuni-negative. These findings suggest that the three phenomena "axonal dysfunctions (AMAN or early-reversible conduction failure)," "IgG antibodies against GM1, GD1a, GalNAc-GD1a, or GD1b," and "C. jejuni infection" are closely associated but that microorganisms other than C. jejuni frequently trigger an anti-ganglioside response and elicit axonal GBS.     

Antiganglioside antibodies in Guillain-Barré syndrome after a recent cytomegalovirus infection

OBJECTIVE: To study the association between anti-ganglioside antibody responses and Guillan-Barré syndrome (GBS) after a recent cytomegalovirus (CMV) infection. METHODS: Enzyme linked immunosorbant assay (ELISA) was undertaken on serum samples from 14 patients with GBS with recent cytomegalovirus (CMV) infection (CMV+GBS) and 12 without (CMV-GBS), 17 patients with other neurological diseases (OND), 11 patients with a recent CMV infection but without neurological involvement, 11 patients with recent Epstein-Barr virus (EBV) infection but without neurological involvement, and 20 normal control (NC) subjects. RESULTS: IgM antibodies were found at 1:100 serum dilution to gangliosides GM2 (six of 14 patients), GM1 (four of 14), GD1a (three of 14) and GD1b (two of 14) in the serum samples of the CMV+GBS patients, but not in those of any of the CMV-GBS patients. IgM antibodies were also found to gangliosides GM1, GD1a, and GD1b in one of 11 OND patients, to ganglioside GM1 in one of 11 non- neurological CMV patients, and to ganglioside GD1b in one of 20 NC subjects. Some patients with EBV infection had IgM antibodies to gangliosides GM1 (five of 11), GM2 (three of 11), and GD1a (two of 11). However, the antibodies to ganglioside GM2 had a low titre, none being positive at 1:200 dilution, whereas five of the CMV+GBS serum samples remained positive at this dilution. CONCLUSION: Antibodies to ganglioside GM2 are often associated with GBS after CMV infection, but their relevance is not known. It is unlikely that CMV infection and anti-ganglioside GM2 antibodies are solely responsible and an additional factor is required to elicit GBS.     

Association of antibodies to ganglioside complexes and conduction blocks in axonal Guillain‐Barré syndrome presenting as acute motor conduction block neuropathy

A close relationship between acute motor conduction block neuropathy and antibodies against the complex of GM1 and GalNAc‐GD1a has been reported. This study investigates the hypothesis that conduction block at the early phase of axonal Guillain‐Barré syndrome (GBS) is also associated with such ganglioside complexes. Sera were obtained from seven French patients with initial evidence of isolated conduction blocks that resolved or progressed to acute motor axonal neuropathy. Serum IgG to asialo‐GM1 and gangliosides of LM1, GM1, GM1b, GD1a, GalNAc‐GD1a, GD1b, GT1a, GT1b, and GQ1b as well as their complexes were measured. Five of seven patients progressed within the first month of disease to AMAN. One patient had IgG antibodies against the complex of asialo‐GM1 and each of the other ganglioside antigens. Another patient carried IgG antibodies against GM1 complex with GM1b, GD1a, and GT1a as well as asialo‐GM1 complex with GD1a and GT1a. None had IgG antibodies against GM1/GalNAc‐GD1a complex. Six patients had IgG against single antigens GM1, GD1a, GalNAc‐GD1a, GD1b, and asialo‐GM1. In three patients, a reduced reaction against GM1/GalNAc‐GD1a complex was observed. The presence of conduction block in axonal GBS is not always associated with anti‐GM1/GalNAc‐GD1a complex antibodies.     

Clinical presentation and outcome of Guillain-Barré and related syndromes in relation to anti-ganglioside antibodies.

We correlated the clinical features of 78 patients with Guillain-Barré syndrome (GBS) or related variants, with the presence of serum antibodies to the gangliosides GM1, GM2, GD1a, GD1b and GQ1b in order to determine whether these antibodies may influence the clinical presentation or outcome of GBS. Sixty-three patients had typical GBS (81%), nine a pure motor form (11%), three a paraparetic form (4%), and three had Miller Fisher syndrome (MFS). IgG or IgM (or both) anti-ganglioside antibodies were found by ELISA in 37% of patients, including 36% with typical, 33% with pure motor and 100% with MFS. Beside the constant occurrence of anti-GQ1b antibodies in patients with MFS (P<0.00001), the other clinical forms were not associated with a specific anti-ganglioside reactivity. Anti-GM1 and anti-GD1a antibodies tended to be associated with a worse disability at 6 month than other or no reactivity and, similarly to anti-GM2 antibodies, with a more frequent respiratory impairment. Anti-GM2 and anti-GD1b antibodies were always associated with typical GBS and, in all but one patient, with a complete recovery; still they were found in only 13 and 3%, respectively, of the patients with this presentation. Anti-GQ1b antibodies, though always associated with ophthalmoplegia and ataxia in both MFS and GBS, were found in only 36 and 26%, respectively, of patients with these symptoms. Even if different anti-ganglioside antibodies tend to be associated with some clinical features possibly suggesting that they may influence the clinical presentation or outcome, with the exception of anti-GQ1b antibodies for ophthalmoplegia and ataxia, they do not permit to predict the clinical presentation or outcome in individual patients.     

An anti-ganglioside antibody-secreting hybridoma induces neuropathy in mice

Immune responses against gangliosides are strongly implicated in the pathogenesis of some variants of Guillain-Barré syndrome (GBS). For example, IgG antibodies against GM1, GD1a, and related gangliosides are frequently present in patients with post-Campylobacter acute motor axonal neuropathy (AMAN) variant of GBS, and immunization of rabbits with GM1 has produced a model of AMAN. However, the role of anti-ganglioside antibodies in GBS continues to be debated because of lack of a passive transfer model. We recently have raised several monoclonal IgG anti-ganglioside antibodies. We passively transfer these antibodies by intraperitoneal hybridoma implantation and by systemic administration of purified anti-ganglioside antibodies in mice. Approximately half the animals implanted with an intraperitoneal clone of anti-ganglioside antibody-secreting hybridoma developed a patchy, predominantly axonal neuropathy affecting a small proportion of nerve fibers. In contrast to hybridoma implantation, passive transfer with systemically administered anti-ganglioside antibodies did not cause nerve fiber degeneration despite high titre circulating antibodies. Blood-nerve barrier studies indicate that animals implanted with hybridoma had leaky blood-nerve barrier compared to mice that received systemically administered anti-ganglioside antibodies. Our findings suggest that in addition to circulating antibodies, factors such as antibody accessibility and nerve fiber resistance to antibody-mediated injury play a role in the development of neuropathy.     

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.     

Ganglioside antibodies: a lack of diagnostic specificity and clinical utility?

Summary Serum IgG and IgM antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b and GT1b were determined in 210 patients with different degenerative and inflammatory disorders including motor neuron diseases, peripheral radiculopathies and neuropathies, multiple sclerosis and neuroborreliosis. No single disorder was associated specifically with ganglioside antibodies. No characteristic patterns of ganglioside antibodies were observed in any disease category. However, 32% of all patients had pathological antibody titres to at least one ganglioside. Four patients had pathological IgG and IgM titres for all gangliosides evaluated. They suffered from systemic lupus erythematosus [2], neuroborreliosis and schizophrenia, respectively. The results of this study indicate that the introduction of ganglioside antibody determination as a differential diagnostic test in clinical neurology is only helpful in a few patients with typical lower motor neuron syndromes.     

Longitudinal changes of anti-ganglioside antibodies before and after Guillain-Barré syndrome onset subsequent to Campylobacter jejuni enteritis

Anti-ganglioside antibodies frequently are present in sera from patients with Guillain–Barré syndrome (GBS) during the acute phase, but no patients in whom anti-ganglioside antibodies were tested before the onset of the syndrome have been reported. We describe the first case of GBS subsequent to Campylobacter jejuni infection, in which longitudinal changes in anti-ganglioside antibody titers were measured before and after the onset of limb weakness. Serum antibody titers against GM1 (IgM/IgG), GM1b (IgM/IgG), GalNAc-GD1a (IgM/IgG), and GD1b (IgG) were highest on the day of onset, but negative before onset. Anti-C. jejuni IgG and IgA antibody titers paralleled those of the anti-ganglioside antibodies, indicative that C. jejuni infection triggered anti-ganglioside antibody production. Press et al. [J. Neurol. Sci. 190 (2001) 41] reported that anti-ganglioside antibody titers peaked during the recovery phase, but our findings are counter to theirs. We speculate that anti-ganglioside antibodies are the primary effectors of nerve damage in GBS.     

GD1b-specific antibodies may bind to complex of GQ1b and GM1, causing ataxia

Monospecific IgG antibodies to GD1b ganglioside (GD1b-specific antibodies) have been found in patients with acute ataxic neuropathy and Guillain–Barré syndrome, but the association of the GD1b-specific antibodies with specific neurological conditions has yet to be established. We tested sera from more than 10,000 patients with various neurological disorders, and found six sera, which contained IgG antibodies to GD1b, but not to LM1, GM1, GM1b, GD1a, GalNAc-GD1a, GT1a, GT1b and GQ1b. All six patients who carried GD1b-specific antibodies presented with acute onset of ataxia and monophasic course of the illness, of whom five demonstrated cerebellar-like ataxia. Four patients had antecedent symptoms of upper respiratory tract infection. The six patients demonstrated areflexia, and four complained of distal numbness. All the six patients who had the GD1b-specific antibodies carried IgG antibodies to complex of GQ1b/GM1 and GT1a/GM1. GD1b-specific antibodies were significantly absorbed by GQ1b/GM1 and GT1a/GM1 and anti-GQ1b/GM1 and -GT1a/GM1 antibodies were absorbed by GD1b. In conclusion, the GD1b-specific antibodies, which recognizes GQ1b/GM1 or GT1a/GM1 complex, are associated with acute ataxia.     

A characteristic ganglioside antibody pattern in the CSF of patients with amyotrophic lateral sclerosis.

Paired cerebrospinal fluid and serum samples of patients with amyotrophic lateral sclerosis (n = 35) revealed no consistent abnormalities of CSF cell count, CSF albumin, CSF IgG, CSF IgM, IgG or IgM index, or oligoclonal immunoglobulin band formation in the CSF. Determination of IgG and IgM CSF and serum antibodies to gangliosides GM1, GM2, GM3, AGM1, GD1a, GD1b, and GT1b showed a characteristic pattern which allowed the differentiation of amyotrophic lateral sclerosis from controls and from patients with other neurological disorders including multiple sclerosis. Specifically, patients with the disease had elevated CSF IgM antibodies to all gangliosides except AGM1. The lack of correlation between the CSF findings and corresponding serum antibodies suggests a chronic, compartmental, intrathecal immune response of low activity in amyotrophic lateral sclerosis. Whether this immune response is primary and of pathogenetic significance, or an epiphenomenon of neuronal degeneration, remains to be investigated.     

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.     

The immunobiology of Guillain-Barré syndromes

This presentation highlights aspects of the immunobiology of the Guillain-Barré syndromes (GBS), the world's leading cause of acute autoimmune neuromuscular paralysis. Understanding the key pathophysiological pathways of GBS and developing rational, specific immunotherapies are essential steps towards improving the clinical outcome of this devastating disorder. Much of the research into GBS over the last decade has focused on the forms mediated by anti-ganglioside antibodies, and we have made substantial progress in our understanding in several related areas. Particular highlights include (a) the emerging correlations between anti-ganglioside antibodies and specific clinical phenotypes, notably between anti-GM1/anti-GD1a antibodies and the acute motor axonal variant and anti-GQ1b/anti-GT1a antibodies and the Miller Fisher syndrome; (b) the identification of molecular mimicry between GBS-associated Campylobacter jejuni oligosaccharides and GM1, GD1a, and GT1a gangliosides as a mechanism for anti-ganglioside antibody induction; (c) the development of rodent models of GBS with sensory ataxic or motor phenotypes induced by immunisation with GD1b or GM1 gangliosides, respectively. Our work has particularly studied the motor nerve terminal as a model site of injury, and through combined active and passive immunisation paradigms, we have developed murine neuropathy phenotypes mediated by anti-ganglioside antibodies. This has been achieved through use of glycosyltransferase and complement regulator knock-out mice, both for cloning anti-ganglioside antibodies and inducing disease. Through such studies, we have proven a neuropathogenic role for murine anti-ganglioside antibodies and human GBS-associated antisera and identified several determinants that influence disease expression including (a) the level of immunological tolerance to microbial glycans that mimic self-gangliosides; (b) the ganglioside density in target tissue; (c) the level of complement activation and the neuroprotective effects of endogenous complement regulators; and (d) the role of calcium influx through complement pores in mediating axonal injury. Such studies provide us with clear information on an antibody-mediated pathogenesis model for GBS and should lead to rational therapeutic testing of agents that are potentially suitable for use in humans.     

Transglutaminase-independent binding of gliadin to intestinal brush border membrane and GM1 ganglioside

Anti-ganglioside antibodies have been described in celiac disease or gluten sensitivity, in conjunction with the presence of central and peripheral nervous system deficits. The observed antibody reactivity to gangliosides is postulated to be related to the anti-gliadin immune response, either through antigenic mimicry, or by formation of gliadin-ganglioside complexes and haptenization. We examined the possibility of the presence of ganglioside-like epitopes in gliadin, as well as the potential for complex formation between gliadin and GM1 ganglioside. Low levels of glycosylation were present in gliadin, but ganglioside-like carbohydrate epitopes were not detected. However, gliadin was found to bind to GM1 ganglioside and to the GM1-rich intestinal brush border membrane. The described complex formation and possible haptenization of GM1 by gliadin may be responsible for driving the anti-ganglioside antibody response in some patients with gluten sensitivity. Furthermore, binding of gliadin to GM1 on the intestinal epithelium might have a role in the anti-gliadin immune response and contribute to the intestinal inflammatory reaction in celiac disease.     

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.     

Antiganglioside antibodies in polyneuropathy associated with monoclonal gammopathy.

Antibody reactivity to GA1, GM1, GM2, GD1a, GD1b, and GQ1b gangliosides was measured in 87 patients with polyneuropathy associated with monoclonal gammopathy (60 IgM, 25 IgG, 2 IgA) and 42 control patients with monoclonal gammopathy without polyneuropathy (21 IgM, 21 IgG). Of these 87 patients, 30% had anti-myelin-associated glycoprotein antibodies and 15% had antiganglioside antibodies. Antiganglioside antibodies were significantly associated with demyelinating neuropathy and with IgM monoclonal gammopathy. Anti-GD1b and anti-GQ1b antibodies were significantly associated with predominantly sensory ataxic neuropathy.     

Anti-ganglioside antibody and neuropathy: review of our research

Some patients developed Guillain-Barré syndrome (GBS) after the administration of bovine gangliosides. Patients with GBS subsequent to Campylobacter jejuni enteritis frequently have IgG antibody to GM1 ganglioside. Fisher's syndrome (FS), a variant of GBS, is associated with IgG antibody to GQ1b ganglioside. We showed the existence of molecular mimicry between GM1 and lipopolysaccharide (LPS) of C. jejuni isolated from a GBS patient, and that between GQ1b and C. jejuni LPSs from FS patients. Several lines of evidence suggest a pathogenic role for anti-ganglioside antibodies. Some patients developed sensorimotor polyneuropathy after anti-GD2 antibody administration. Anti-GM1 antibody can block motor nerve conduction. The molecular mimicry between infectious agents and gangliosides may function in the production of anti-ganglioside antibodies and the development of GBS and FS. Anti-GQ1b IgG antibody is detected also in Bickerstaff's brainstem encephalitis and acute ophthalmoparesis, which suggests that these conditions are categorized as autoimmune diseases related to FS. Since a tryptophan-immobilized column effectively adsorb anti-GQ1b IgG antibody, immunoadsorption with the column should be considered as an alternative form of plasmapheresis for the anti-GQ1b IgG antibody syndrome.