IgG Anti-ganglioside Antibodies Research Articles

Tumor necrosis factor α receptor 1A transduces the inhibitory effect on axon regeneration triggered by IgG anti-ganglioside GD1a antibodies

Anti-ganglioside antibodies (anti-Gg Abs) have been linked to delayed/poor clinical recovery in both axonal and demyelinating forms of Guillain-Barrè Syndrome (GBS). In many instances, the incomplete recovery is attributed to the peripheral nervous system's failure to regenerate. The cross-linking of cell surface gangliosides by anti-Gg Abs triggers inhibition of nerve repair in both in vitro and in vivo axon regeneration paradigms. This mechanism involves the activation of the small GTPase RhoA, which negatively modulates the growth cone cytoskeleton. At present, the identity/es of the receptor/s responsible for transducing the signal that ultimately leads to RhoA activation remains poorly understood. The aim of this work was to identify the transducer molecule responsible for the inhibitory effect of anti-Gg Abs on nerve repair. Putative candidate molecules were identified through proteomic mass spectrometry of ganglioside affinity-captured proteins from rat cerebellar granule neurons (Prendergast et al., 2014). These candidates were evaluated using an in vitro model of neurite outgrowth with primary cultured dorsal root ganglion neurons (DRGn) and an in vivo model of axon regeneration. Using an shRNA-strategy to silence putative candidates on DRGn, we identified tumor necrosis factor receptor 1A protein (TNFR1A) as a transducer molecule for the inhibitory effect on neurite outgrowth from rat/mouse DRGn cultures of a well characterized mAb targeting the related gangliosides GD1a and GT1b. Interestingly, lack of TNFr1A expression on DRGn abolished the inhibitory effect on neurite outgrowth caused by anti-GD1a but not anti-GT1b specific mAbs, suggesting specificity of GD1a/transducer signaling. Similar results were obtained using primary DRGn cultures from TNFR1a-null mice, which did not activate RhoA after exposure to anti-GD1a mAbs. Generation of single point mutants at the stalk region of TNFR1A identified a critical amino acid for transducing GD1a signaling, suggesting a direct interaction. Finally, passive immunization with an anti-GD1a/GT1b mAb in an in vivo model of axon regeneration exhibited reduced inhibitory activity in TNFR1a-null mice compared to wild type mice. In conclusion, these findings identify TNFR1A as a novel transducer receptor for the inhibitory effect exerted by anti-GD1a Abs on nerve repair, representing a significant step forward toward understanding the factors contributing to poor clinical recovery in GBS associated with anti-Gg Abs.

Can Serum IgG Antiganglioside Antibodies to GM1, GM3 and GD1a be Used as Markers in Patients with Ischemic Stroke?

Can Serum IgG Antiganglioside Antibodies to GM1, GM3 and GD1a be Used as Markers in Patients with Ischemic Stroke?

Serum antiganglioside antibodies in patients with autoimmune limbic encephalitis.

Ganglioside antibodies are identified not only in patients with inflammatory neuropathies but also several central nervous system disorders and paraneoplastic neuropathies. Our aim was to investigate whether ganglioside antibodies are found in autoimmune encephalitis patients and may function as a diagnostic and prognostic biomarker. Sera and cerebrospinal fluid (CSF) samples of 33 patients fulfilling the criteria for probable autoimmune encephalitis were collected within the first week of clinical manifestation. None of the patients had evident symptoms and findings of peripheral polyneuropathy. Well-characterized antineuronal and paraneoplastic antibodies were investigated in sera and CSF and antiganglioside (antiGM1, GM2, GM3, GD1a, GD1b, GT1b, and GQ1b) IgG and IgM antibodies were measured in sera using commercial immunoblots. Twenty-eight of 33 autoimmune encephalitis patients displayed antibodies against neuronal surface or onco-neural antigens with N-methyl-D-aspartate receptor (NMDAR), glutamic acid decarboxylase (GAD) and Hu antibodies being the most prevalent. While no antiganglioside IgG antibodies were found, 4 patients (2 anti-NMDAR+, 1 anti-GAD+ and 1 antibody negative) with autoimmune limbic encephalitis displayed anti-GM1, anti-GM2, anti-GM3 or anti-GQ1b IgM antibodies. There was no apparent association between antiganglioside positivity and clinical and demographic features. Serum ganglioside IgM antibodies may infrequently emerge during the clinical course of autoimmune limbic encephalitis without evident polyneuropathy. Absence of the IgG response suggests that these antibodies might have developed as a hyperacute immune response to neuro-axonal destruction. Nevertheless, potential impact of ganglioside antibodies on axonal degeneration and neuronal loss in limbic encephalitis pends to be further investigated.

Antiganglioside Antibodies and Inflammatory Response in Cutaneous Melanoma.

Introduction Endogenously produced antiganglioside antibodies could affect the evolution of cutaneous melanoma. Epidemiological and experimental evidence suggest “chronic inflammation” to be one of the hallmarks in skin cancers. The aim of the study was to characterize the relation between antiganglioside antibodies and inflammation in cutaneous melanoma focusing on gangliosides GM1, GM2, GM3, GD1a, GD1b, GT1b, GQ1b. Material and Method. We performed an observational study that included 380 subjects subdivided into three groups: patients with metastatic melanoma (170 cases), patients with primary melanoma (160 cases), and healthy subjects (50 subjects). The assessment of antiganglioside antibodies, IgG, and IgM classes, against -GM1, -GM2, -GM3, -GD1a, -GD1b, -GT1b, -GQ1b was performed using immunoblot technique (EUROLine kit). Results The presence of IgG and IgM antiganglioside antibodies in primary melanoma was (%), as follows: anti-GM1 (5.0 and 13.1), -GM2 (1.8 and 18.1), -GM3 (0.6 and 5.6), -GD1a (0.6 and 15.0), -GD1b (3.7 and 10.7), -GT1b (0.0 and 13.1), -GQ1b (0.0 and 5.0). In metastatic melanoma, the level of antiganglioside antibodies was significantly lower compared with primary melanoma (p < 0.05), while in the control group they were absent. Antiganglioside antibodies anti-GM1 and -GD1a were positively correlated, while anti-GM3, -GD1b, and -GT1b were negatively associated with the inflammatory markers, interleukin 8 (IL-8), and C reactive protein (CRP). Conclusions Tumour ganglioside antigens generate an immune response in patients with primary melanomas. The host's ability to elaborate an early antiganglioside response could be considered as a defence mechanism, directed toward eliminating a danger signal from the tumour microenvironment. Antiganglioside antibodies associated with inflammation markers could be used as diagnostic, monitoring, and treatment tools in patients with cutaneous melanoma.

Prevalence of antibodies to ganglioside and Hep 2 in Gaucher, Niemann – Pick type C and Sanfilippo diseases

Lysosomal Storage Diseases (LSDs) are rare genetic diseases, the majority of which are caused by specific lysosomal enzyme deficiencies and all are characterized by malfunctioning lysosomes. Lysosomes are key regulators of many different cellular processes and are vital for the function of the immune system. Several studies have shown the coexistence of LSDs and immune abnormalities. In this study, we investigated the presence of autoantibodies in the plasma of patients with Gaucher disease (GD; n = 6), Sanfilippo Syndrome B (SFB; n = 8) and Niemann – Pick type C disease (NPC; n = 5) before and following Miglustat treatment (n = 3). All were examined for antibodies to antigens of Hep-2 cells and antiganglioside antibodies (AGSA). No autoantibodies were detected in GD patients. 3/8 SFB patients showed only AGSA (2/3 IgM / IgG; 1/3 IgG), 3/8 only anti-Sm E/F and 2/8 showed both IgM / IgG or IgG AGSA and anti-Sm E/F. 3/5 NPC patients showed AGSA (2/3 IgM and IgG, 1/3 IgM) and one anti-Sm E/F and IgM AGSA. Following treatment one patient with no AGSA developed IgM AGSA and two with both IgG and IgM showed only IgG AGSA. In our study, investigating similar numbers of patients, autoantibodies were observed in NPC and SFB patients but not in GD patients. Our findings suggest that, independently of the development of an autoimmune disease in patients with LSDs, there seems to be an autoimmune activation that differs in different disorders. Further studies including more patients, also at different stages of disease and treatment, are needed in order to get further insight into the immune irregularities associated with different LSDs and their significance.

Guillain-Barré syndrome following varicella-zoster virus infection

We describe the frequency, clinical features, and electrophysiological and immunological phenotypes of Guillain-Barré Syndrome (GBS) patients treated at a single institution in Bangladesh who had preceding chicken pox (primary Varicella-zoster virus [VZV] infection) within 4weeks of GBS onset. A literature review of GBS cases preceding VZV infection is also provided. Diagnosis of GBS was based on the National Institute of Neurological Disorders and Stroke criteria for GBS. Serum anti-VZV IgM and IgG antibodies were quantified by indirect chemiluminescence immunoassay (CLIA); anti-Campylobacter jejuni IgG, IgM, and IgA antibodies and anti-ganglioside GM1 IgM and IgG antibodies, by enzyme-linked immunosorbent assays. Neurophysiologic subtypes were categorized following the Hadden criteria. Of 536 patients with GBS, 7 (1.3%) had chicken pox within 4weeks before GBS onset. Four of the seven cases were male (age range, 23 to 40years old). All seven patients were bed-bound, six had sensory symptoms, and three required mechanical ventilation for respiratory failure. All seven patients had CSF albuminocytologic dissociation and evidence of demyelination in nerve conduction studies. Anti-VZV IgM antibodies were present and anti-GM1 and anti-Campylobacter jejuni lipo-oligosaccharides (LOS) were negative in all cases. All patients had excellent outcome at 1year (able to run). A systematic literature review of GBS cases related to VZV revealed 39 previously reported patients with comparable clinical presentations and outcomes, of which 36 had neurophysiologic evidence of demyelination. VZV infection is associated with the demyelinating subtype of GBS, clearly distinct from the axonal form of GBS that predominate in countries like Bangladesh.

Experimental Guillain-Barre syndrome induced by immunization with gangliosides: Keyhole limpet hemocyanin is required for disease triggering

An experimental model of Guillain-Barré Syndrome has been established in recent years. Rabbits develop disease upon immunization with a single dose of an emulsion containing bovine brain gangliosides, KLH and complete Freund's adjuvant. Within a period of four to ten weeks after immunization, they began to produce anti-ganglioside IgG-antibodies first, and to show clinical signs of neuropathy afterwards. In addition to gangliosides, KLH is a requirement for antibody production and disease triggering. Although KLH is commonly used as an immunological carrier protein, an anti-KLH-specific immune response was necessary for induction of both events. KLH is a glycoprotein carrying most of the immunogenicity in its glycan moiety. Between 20% to 80% of anti-ganglioside IgG-antibodies present in sick rabbit sera cross-reacted with KLH, indicating that both immune responses are related. The terminal Gal-ß(1,3)-GalNAc glycan (present in gangliosides and KLH) is proposed as “key” antigenic determinant involved in inducing the anti-ganglioside immune response. These results are discussed in the context of the “binding site drift” hypothesis.

Anti-ganglioside antibodies profile in Guillain-Barré syndrome: Correlation with clinical features, electrophysiological pattern, and outcome.

Guillain-Barré syndrome (GBS) and its subtypes are associated with distinct anti-ganglioside antibodies. Hence, we aimed to determine the frequency of anti-ganglioside antibodies and its correlation with clinical features, electrophysiological patterns, and outcome in patients with GBS. The data regarding clinical features, electrophysiological patterns, and outcome at 6 months were collected and analyzed from the case records of patients diagnosed with GBS during 2008-2013 at a tertiary care hospital in south India. A total of 204 patients with GBS were studied, and 73 patients (mean age: 37.6 ± 17.5 years) who underwent anti-ganglioside antibody testing were analyzed. Male-to-female ratio was 2.5:1. IgG anti-ganglioside antibodies were positive in 41/73 patients. The most common IgG anti-ganglioside antibody observed in the acute demyelinating variant was anti-GT1b (n = 13; 17.8%), and, those in the acute axonal variant were anti-GM1, anti-GM2, anti-GD1b, and anti-GT1b antibodies (n = 9;12.3% each). Three patients died and 5 patients were unable to walk independently at the end of 6 months. The frequency of anti-ganglioside antibodies in our cohort with GBS was 56%, with IgG anti-GT1b antibody being the most common. The anti-ganglioside antibodies were significantly positive in acute motor axonal neuropathy (AMAN) subtype of GBS. The presence of anti-ganglioside antibodies was not found to be of significant use in predicting the outcome. Although it was observed that the absence, and not the presence, of anti-ganglioside antibodies was associated with antecedent infection, dysautonomia, and requirement of ventilator support, the overall disease severity was not antibody dependant.

Anti-ganglioside antibodies in Guillain-Barré syndrome and chronic inflammatory demyelinating polyneuropathy in Chinese patients.

In this study we investigated the relationships between anti-ganglioside antibodies and Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP). Samples from 48 Chinese patients diagnosed with GBS and 18 patients diagnosed with CIDP were retrospectively reviewed. In the GBS patients, 62.5% were classified as having acute inflammatory demyelinating polyneuropathy (AIDP), 27.1% were found to have acute motor axonal neuropathy (AMAN), and 10.4% were unclassified. Serum IgG anti-ganglioside antibodies were detected in 46.2% of the AMAN patients and in 6.7% of the AIDP patients (P < 0.05); 5.6% of the 18 CIDP patients were IgG antibody positive, and 27.8% were IgM antibody positive. Facial palsy and sensory impairment were significantly associated with IgM antibodies. These results suggest that IgG anti-GM1 antibodies are associated with AMAN, but not with AIDP, and that IgM antibodies against GM1, GM2, and GM3 are associated with facial nerve palsy. Muscle Nerve 55: 470-475, 2017.

Isolated facial diplegia in Guillain–Barré syndrome: Bifacial weakness with paresthesias

Bifacial weakness with paresthesias (BFP) is a subtype of Guillain-Barré syndrome defined by rapidly progressive bilateral facial weakness in the absence of other cranial neuropathies, ataxia, or limb weakness. Many patients also complain of distal limb paresthesias and display diminished or absent deep tendon reflexes. BFP is a localized form of Guillain-Barré syndrome and is thought to be caused exclusively by demyelinating- rather than axonal-type neuropathy. Patients with BFP do not display anti-ganglioside IgG antibodies. Since it is rare, many physicians are unfamiliar with BFP, as bilateral facial weakness is more commonly associated with sarcoidosis, Lyme disease, or meningeal pathology. Many patients diagnosed with bilateral Bell palsy may instead have BFP. In this review, we highlight the clinical features of BFP and outline diagnostic criteria.

Autoantibodies against ganglioside GM3 are associated with narcolepsy-cataplexy developing after Pandemrix vaccination against 2009 pandemic H1N1 type influenza virus

Following the mass vaccinations against pandemic influenza A/H1N1 virus in 2009, a sudden increase in juvenile onset narcolepsy with cataplexy (NC) was detected in several European countries where AS03-adjuvanted Pandemrix vaccine had been used.NC is a chronic neurological disorder characterized by excessive daytime sleepiness and cataplexy. In human NC, the hypocretin-producing neurons in the hypothalamus or the hypocretin signaling pathway are destroyed by an autoimmune reaction. Both genetic (e.g. HLA-DQB1*0602) and environmental risk factors (e.g. Pandemrix) contribute to the disease development, but the underlying and the mediating immunological mechanisms are largely unknown.Influenza virus hemagglutinin is known to bind gangliosides, which serve as host cell virus receptors. Anti-ganglioside antibodies have previously been linked to various neurological disorders, like the Guillain-Barré syndrome which may develop after infection or vaccination. Because of these links we screened sera of NC patients and controls for IgG anti-ganglioside antibodies against 11 human brain gangliosides (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b) and a sulfatide by using a line blot assay. Samples from 173 children and adolescents were analyzed: 48 with Pandemrix-associated NC, 20 with NC without Pandemrix association, 57 Pandemrix-vaccinated and 48 unvaccinated healthy children. We found that patients with Pandemrix-associated NC had more frequently (14.6%) anti-GM3 antibodies than vaccinated healthy controls (3.5%) (P = 0.047). Anti-GM3 antibodies were significantly associated with HLA-DQB1*0602 (P = 0.016) both in vaccinated NC patients and controls. In general, anti-ganglioside antibodies were more frequent in vaccinated (18.1%) than in unvaccinated (7.3%) individuals (P = 0.035). Our data suggest that autoimmunity against GM3 is a feature of Pandemrix-associated NC and that autoantibodies against gangliosides were induced by Pandemrix vaccination.

Streptococcal IdeS: therapeutic potential for Guillain-Barré syndrome.

Plasma exchange and intravenous immunoglobulin are effective in treating Guillain–Barré syndrome (GBS) probably because the former removes IgG autoantibodies and complement and the latter inhibits complement activation subsequent to the autoantibody binding to peripheral nerve antigens. IgG degrading enzyme of Streptococcus pyogenes (IdeS) can cleave the pathogenic autoantibodies into F(ab’)2 and Fc. The purpose of this study is to show whether IdeS has novel therapeutic potential for GBS. Sera with anti-ganglioside IgG antibodies from 15 patients with GBS or Miller Fisher syndrome were used. We tested whether IdeS cleaved the anti-ganglioside IgG antibodies and inhibited deposition of activated complement component on ELISA plates. IdeS efficiently cleaved IgG and blocked complement activation mediated by anti-GM1, anti-GD1a and anti-GQ1b IgG antibodies. IdeS has therapeutic potential for GBS and related conditions.

Comparison of Commercial Tests for Detecting Multiple Anti-Ganglioside Autoantibodies in Patients with Well-Characterized Immune-Mediated Peripheral Neuropathies

To assess the performance of commercial anti-ganglioside antibody assays, we determined anti-ganglioside antibody IgG and IgM isotype profiles of patients with acute and chronic well-characterized immune-mediated peripheral neuropathies by one immunodot assays (Zentec/Ingen: Dotzen Ganglio Profile Ab, Euroimmun/BioAdvance: Euroline ganglioprofile), two line-immuno assay (GA Generic Assays/Labodia: Anti-Gangli osid Dot, Euroimmun/BioAdvance: Euroline ganglioprofile), and one enzyme-linked immunosorbent assay (ELISA) (Bühlmann: GanglioCombi). Specific antibody profiles were compared with those obtained by our validated standard in-house immunodot assay (IDA). We selected 33 sera with high levels of IgG and IgM anti-ganglioside antibodies from 15 patients with Guillain-Barre syndrome (GBS) subtypes and variants, 12 patients with CANOMAD syndrome (chronic ataxic neuropathy with ophthalmoplegia, M-paraprotein, cold agglutinins, disialosyl antibodies), 5 patients with chronic motor peripheral neuropathies, and 1 patient with sensory neuropathy and a control group composed of 10 patients with non-autoimmune neuropathy. The 3 commercial IDAs employing hydrophobic membranes and the ELISA demonstrated different carbohydrate epitopes on 6 to 12 glycolipid antigens used for anti-ganglioside antibody detection. Comparison with the validated in-house IDA showed large variations in sensitivity between tests and a more diverse reactivity to gangliosides than expected. The test with the largest panel of glycolipids detecting 11 anti-ganglioside antibody reactivities (GM1, GM2, GM3, GM4, GD1a, GD1b, GD2, GD3, GT1a, GT1b, GQ1b, and sulfatide) revealed the best concordance with our in-house assay. However, even with this test, differences were observed in the immunoreactivity against some gangliosides and weakly stained bands were not easy to interpret. Our data suggest an urgent need for standardization of commercial anti-ganglioside assays and the introduction of international anti-ganglioside antibody reference standards.

A-waves in Guillain–Barré syndrome: Correlation with electrophysiological subtypes and antiganglioside antibodies

ObjectiveTo investigate the relationship of A-waves with conventional electrophysiological subtypes of Guillain–Barré syndrome (GBS), as well as with anti-ganglioside antibodies. MethodsThe subjects consisted of 30GBS patients who were classified into acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy, and unclassified based on the results of nerve conduction studies. “Abundant A-waves” were defined for the upper-limb nerves (median and ulnar nerves) using receiver–operator characteristic curves. The presence or absence of IgG anti-ganglioside antibodies was also noted. ResultsAbundant A-waves at weeks 3–6 from onset were observed in 64% of the 14 AIDP patients and 0% of 16 non-AIDP patients, and in 60% of 15 antibody-negative patients and 0% of 15 antibody-positive patients. In the earlier period, this relationship was less clear. The correlation between the conventional electrophysiological subtypes and antibodies was present, but was much weaker. ConclusionsAbundant A-waves in GBS after the acute phase were strongly associated with demyelination that was not mediated by antiganglioside antibodies, possibly through the mechanism of proximal re-excitation induced by electrical inhomogeneities due to segmental demyelination. SignificanceAbundant A-waves are promising as a novel reliable marker of demyelination.

BAFF aids generation of IgG anti-ganglioside antibodies in response to Campylobacter jejuni lipo-oligosaccharide

Ganglioside mimicry of Campylobacter jejuni lipo-oligosaccharide (LOS) can induce the production of IgG anti-ganglioside antibodies, but the generation mechanism has yet to be clarified. B-cell activating factor belonging to the TNF family (BAFF) helped murine B cells produce anti-ganglioside antibodies against C. jejuni LOS. In splenocyte culture, however, anti-ganglioside antibodies were produced in the presence of a soluble transmembrane activator and calcium-modulating and cyclophilin ligand interactor immunoadhesin (TACI-Ig), a receptor for BAFF. TACI-Ig adenoviral vectors failed to decrease production of anti-ganglioside antibodies in mice sensitized with C. jejuni LOS and did not alter IgG subclasses, evidence that BAFF aids but is not essential for the generation of IgG anti-ganglioside antibodies in response to C. jejuni LOS.

Ganglioside mimicry and peripheral nerve disease

Four criteria must be satisfied to conclude that a given microorganism causes Guillain-Barré (GBS) or Fisher (FS) syndrome associated with anti-ganglioside antibodies: (1) an epidemiological association between the infecting microbe and GBS or FS; (2) isolation in the acute progressive phase of illness of that microorganism from GBS or FS patients with associated anti-ganglioside IgG antibodies; (3) identification of a microbial ganglioside mimic; and (4) a GBS or FS with associated anti-ganglioside antibodies model produced by sensitization with the microbe itself or its component, as well as with ganglioside. Campylobacter jejuni is a definitive causative microorganism of acute motor axonal neuropathy and may cause FS and related conditions. Haemophilus influenzae and Mycoplasma pneumoniae are possible causative microorganisms of acute motor axonal neuropathy or FS. Acute and chronic inflammatory demyelinating polyneuropathies may be produced by mechanisms other than ganglioside mimicry.

Neurological Complications of Celiac Disease and Autoimmune Mechanisms: Preliminary Data of a Prospective Study in Adult Patients

Antibodies to gangliosides and Purkinje cells have been reported in patients with celiac disease (CD) with neuropathy and ataxia, respectively. Whether these antibodies are pathogenic is not clear. The response of neurological symptoms and antibody titers to a gluten-free diet is still controversial. The objective of our study was to assess whether neurological manifestations in CD patients correlate with antibody titers and a gluten-free diet.Thirty-five CD patients (9 males, 26 females, mean age 37.1 +/- 12.6 yrs) were followed prospectively. At initial evaluation, 23 were on a gluten-free diet, 12 were not. At recruitment and during follow-up, patients underwent neurological and electrophysiological evaluation. IgG, IgM, and IgA anti-ganglioside antibodies were assayed by ELISA; anti-neuronal antibodies were assessed by immunohistochemistry and Western blot. Four patients, all males, had electrophysiological evidence of neuropathy; three had been on a gluten-free diet for several months, and one was newly diagnosed. One had reduced tendon reflexes; another complained of distal paresthesias. With regard to anti-ganglioside antibodies, three patients had a moderate increase in antibodies without symptoms or signs of neuropathy. No patients had ataxia or cerebellar dysfunction, although in four patients reactivity to neuronal antigens was found. In 17 patients, an electrophysiological follow-up (mean duration of follow-up, 9 months) showed no changes. In conclusion, the preliminary results of this prospective study indicate that neuropathy, usually subclinical, may accompany CD. Antibody titers do not seem to correlate with neurological symptoms/signs or diet. Ongoing follow-up will help confirm these data and clarify the role, if any, of antibodies in neurological involvement in CD.

CDR3 spectratyping analysis of the T cell receptor repertoire in Guillain–Barré and Fisher syndromes

Several autoimmune and infectious disorders show oligoclonal expansion of particular T cell phenotypes. The extent of T cell involvement in the pathogenesis of Guillain–Barré syndrome (GBS), a post-infectious autoimmune neuropathy, however, is not clear. To identify the pathogenic T cell phenotypes in GBS and Fisher syndrome (FS), variations in T cell receptor use of the Vβ1-24 and Vδ1-5 chain genes were analyzed at complementarity-determining region 3 level in 119 patients with GBS or FS. Overall, Vβ and Vδ spectratypes were expanded more frequently in patients with GBS (Vβ in 77%, Vδ in 53%) or FS (Vβ in 75%, Vδ in 65%) than in the healthy controls (Vβ in 59%, Vδ in 38%). No particular spectratype was significantly associated with GBS or FS. Subgrouping the patients by Campylobacter jejuni serology and anti-ganglioside IgG antibodies also failed to detect particular spectratype gene use. The frequency of Vβ5.2 expansion tended to be higher in patients with positive Haemophilus influenzae serology (50%) than in the controls (7%), but the difference was not significant. Our findings show that oligoclonal expansion of T cells bearing particular type T cell receptor Vβ and Vδ genes frequently occurs in GBS and FS, suggestive that T cells mediate the development of these neuropathies. The predominant phenotypes vary, even within subgroups of patients with a syndrome of single etiological origin or those with uniform serological features.

Anti-GM1 IgG antibodies induce leukocyte effector functions via Fcgamma receptors.

Guillain-Barré syndrome (GBS) is an immune-mediated neuropathy, in which leukocytes and humoral components of the immune system proposedly initiate localized inflammation. An important pathogenic role for anti-GM1 ganglioside antibodies has been suggested. Therefore, we evaluated anti-GM1 IgG antibody-induced leukocyte effector functions such as degranulation and phagocytosis using serum of 24 GBS patients. Serum without anti-GM1 antibodies of 9 GBS patients as well as pooled serum from healthy individuals served as controls. Ten out of 15 (67%) of anti-GM1 IgG positive sera were capable of inducing leukocyte degranulation, and 8 out of 15 (53%) of anti-GM1 IgG positive sera were capable of inducing phagocytosis of GM1-coated beads. In all of these sera anti-GM1 antibody titers were >or=1:800. No leukocyte degranulation or phagocytosis was observed in control sera. Leukocyte activation was completely abrogated in the presence of IgG receptor (FcgammaR) blocking antibodies, suggesting a crucial role for leukocyte FcgammaR in GBS pathogenesis. No correlation of antibody titers with the extent of leukocyte activation, or severity of disease was observed. These data document the capacity of anti-GM1 IgG antibodies to activate leukocyte inflammatory functions, and suggest an important role for anti-ganglioside IgG antibodies in the pathogenesis of GBS.

IGG ANTIGANGLIOSIDE ANTIBODIES IN GUILLAIN‐BARRE SYNDROME WITH BULBAR PALSY

Some patients with Guillain‐Barre syndrome (GBS) develop bulbar palsy, which may lead to serious complications during the acute phase of the illness. A serological marker that could predict the occurrence of bulbar palsy would be valuable for the treatment of acute GBS. We examined the serum levels of various IgG antiganglioside antibodies in the sera of 16 patients with GBS with bulbar palsy [GBS‐BP(+)] and 72 patients with CBS without bulbar palsy [GBS‐BP(‐)]. Anti‐GT1a antibodies were detected in a higher percentage of the GBS‐BP(+) patients (10/16, 63%) than the GBS‐BP(−) patients (2/72, 3%). In addition to GT1a, a new disialosylganglioside antigen was recognized by the sera of four GBS‐BP(+) patients. Anti‐GM1b antibodies were also frequently detected in the sera of the GBS‐BP(+) cases. However, anti‐GM1 and anti‐GalNAc‐GD1a antibodies, which are highly associated with acute axonal motor neuropathy (AMAN), were not detected in any of the GBS‐BP(+) cases, while anti‐GM1 antibodies were detected in 29% (21/72) and anti‐GalNAc‐GD1a antibodies were detected in 8% (6/73) of the GBS‐BP(−) cases. These findings suggest that the presence of particular antiganglioside antibodies might be related with certain clinical manifestations of GBS. In patients who are diagnosed with GBS, the presence or absence of anti‐GT1a and anti‐GM1b antibodies should be tested at the early stage of GBS so that appropriate therapies that prevent the development of bulbar palsy and improve the outcome of GBS, may be initiated.