Biological roles of anti-GM1 antibodies in patients with Guillain-Barré syndrome for nerve growth factor signaling

To reveal the biological and pathological roles of anti-GM1 antibody in Guillain-Barré syndrome (GBS), we examined its effects on nerve growth factor (NGF) induced TrkA autophosphorylation (NGF-TrkA signaling) in PC12 cells, a sympathetic nerve cell line. The NGF-TrkA signaling is enhanced by exogenous GM1 ganglioside and this phenomenon is regarded as one of the functional aspects of GM1. The IgGs purified from patients' sera inhibited the NGF-TrkA signaling in GM1 pre-incubated PC12 cells. The degrees of inhibition by IgGs from patients paralleled their immunological reactivity to GM1. In addition, the IgGs also inhibited the neurite outgrowth of NGF-treated PC12 cells. Immunoglobulins in the rabbit sera, which were immunized by GM1, also caused a similar suppressive phenomenon. These results suggested that the anti-GM1 antibody could play roles in pathophysiology in anti-GM1 antibody positive GBS through interfering with the neurotrophic action of NGF and GM1 mediated signal modulation including NGF-TrkA signaling. It is suggested that the modulation of GM1 function is one important action of antibodies and could be one of the important mechanisms in GBS.     

Outbreak of Guillain-Barré syndrome associated with water pollution.

Sixteen cases of Guillain-Barré syndrome occurred in the third week of a diarrhoea epidemic caused by water pollution in EL-Sult, Jordan. Of 30 000 people exposed to polluted water, 5000 developed diarrhoea, 74 typhoid, and 30 infectious hepatitis. Thirteen of the 16 patients with Guillain-Barré syndrome had been mildly affected by diarrhoea 8-24 days before the onset of peripheral neuropathy. Paralysis progressed rapidly, reaching a peak in one to five days, and recovery began three to seven days after the start of the most severe symptoms. All but four patients had recovered completely after one year. Rapid progress of paralysis and a delayed interval between maximum weakness and start of recovery were both associated with poor prognosis.     

Mannose-binding lectin contributes to the severity of Guillain-Barré syndrome

In Guillain-Barré syndrome (GBS), complement activation plays a crucial role in the induction and extent of the postinfectious immune-mediated peripheral nerve damage. Mannose-binding lectin (MBL) activates the complement system via the lectin pathway after recognition of repetitive sugar groups on pathogens. We investigated whether the MBL2 genotype, serum MBL level, and MBL complex activity are associated with the development and severity of GBS. Single nucleotide polymorphisms in the promoter region (-550 H/L and -221 X/Y) and exon 1 (A/O) of the MBL2 gene were determined in 271 GBS patients and 212 healthy controls. The frequencies of the H allele, HY promoter haplotype, and HYA haplotype, which are related to high MBL activity, were all increased in GBS patients compared with healthy controls (p < or = 0.03), particularly in severely affected GBS patients (MRC-sum score < 40) (p < or = 0.02). Severe weakness was also associated with high MBL concentrations and MBL complex activity in sera from GBS patients (p < 0.01). The MBL2 B allele was associated with functional deficiency and relatively mild weakness. These results support the hypothesis that complement activation mediated by MBL contributes to the extent of nerve damage in GBS, which is codetermined by the MBL2 haplotype.     

Construction of rat spinal cord injury model based on Allen’s animal model

The aim of this study is to explore the construction of rat spinal cord injury model guided by Allen's model. Methods: Male rats aged 4–5 weeks and weighing about 250 g are selected as subjects in the Animal Laboratory Center of XX Hospital. Rats are divided into two groups, which are experimental group 1 and experimental group 2, respectively, so as to construct spinal cord injury model in rats. The first group is given 300 g.cm hitting force of T10 spinal cord, and the second group is given 500 g.cm hitting force of T10 spinal cord. Within 25 days after spinal cord injury in Allen's rats, the survival, neurological function, diet, motor ability, tactile ability and auditory ability of the two groups are monitored and evaluated daily. Results: In terms of survival, the survival rate of rats in group 1 is 85%, while that of rats in group 2 is 21%, and there is a concentrated death phenomenon in group 2. In terms of neurological function recovery, experimental group 1 is stable and gets 7 points and experimental group 2 is stable and gets 3 points. In terms of diet, the experimental group 1 is stable and gets 5 points and the experimental group 2 is stable and gets 2 points. In terms of motor ability, the experimental group 1 is stable and gets 5 points and the experimental group 2 is stable and gets 2 points. In tactile sense, experimental group 1 is stable and gets 17 points and experimental group 2 is stable and gets 12 points. It can be seen that the post-operative recovery ability of the experimental group 1 is better than that of the experimental group 2. Conclusion: Under the guidance of Allen's model, compared with the group 2, the experimental group 1 of the rat spinal cord injury model has better recovery in each index. It can be seen that the smaller impact strength is more beneficial to the recovery of rats after spinal cord injury surgery.     

Antibodies against ganglioside complexes in Guillain-Barré syndrome and related disorders

Guillain-Barré syndrome (GBS) is acute autoimmune neuropathy, often subsequent to an infection. Serum anti-ganglioside antibodies are frequently elevated in titer. Those antibodies are useful diagnostic markers and possible pathogenetic factors. Recent data demonstrated that sera from some patients with GBS react with ganglioside complexes (GSCs) consisting of two different gangliosides, but not with each constituent ganglioside. Those antibodies may specifically recognize a new conformational epitope formed by two gangliosides. In particular, the antibodies against GD1a/GD1b and/or GD1b/GT1b complexes are associated with severe GBS requiring artificial ventilation. The antibodies to GM1/GalNAc-GD1a and those to GSCs containing GQ1b or GT1a are associated with pure motor GBS and Fisher syndrome, respectively. In contrast, the binding activities of the antibodies highly specific to GD1b are strongly inhibited by the addition of GD1a to GD1b. Gangliosides along with other components as cholesterol are known to form lipid rafts, in which two different gangliosides may form a new conformational epitope. Future investigation is necessary to elucidate the roles of GSCs in the plasma membrane and of the clinical relevance of the anti-GSCs antibodies.     

Activated terminal complement in cerebrospinal fluid in Guillain-Barré syndrome and multiple sclerosis

A quantitative enzyme-linked immunosorbent assay was used to measure the concentration of fluid-phase complement C5b-9 complexes (SC5b-9) in the cerebrospinal fluid (CSF) of 14 patients with acute monophasic Guillain-Barré Syndrome (GBS), 21 patients with multiple sclerosis (MS), and 11 patients with noninflammatory central nervous system (CNS) diseases. SC5b-9 complexes were detected in the CSF of 13 of 14 patients with acute GBS (mean, 3.08 micrograms/ml; range, 0 to 7.1 micrograms/ml) and 16 of 21 patients with MS (mean, 1.83 micrograms/ml; range, 0 to 7.5 micrograms/ml). In the control group of patients with noninflammatory CNS diseases, SC5b-9 was not detected in eight of 11 and was present in low concentrations in the remaining three patients (mean, 0.28 micrograms/ml; range, 0 to 1.7 micrograms/ml). The finding of SC5b-9 complexes in the CSF of patients with GBS and MS suggests that terminal complement components may participate in the tissue-damaging processes in these diseases.     

Antibodies against gangliosides and ganglioside complexes in Guillain-Barré syndrome: new aspects of research

Guillain-Barré syndrome (GBS) is an acute autoimmune neuropathy, often preceded by an infection. Serum anti-ganglioside antibodies are frequently elevated in titer. Those antibodies are useful for diagnosis. Some of them also may be directly involved in the pathogenetic mechanisms by binding to the regions where the respective target ganglioside is specifically localized. We have recently found the presence of the antibody that specifically recognizes a new conformational epitope formed by two gangliosides (ganglioside complex) in the acute-phase sera of some GBS patients. In particular, the antibodies against GD1a/GD1b and/or GD1b/GT1b complexes are associated with severe GBS requiring artificial ventilation. Some patients with Miller Fisher syndrome also have antibodies against ganglioside complexes including GQ1b; such as GQ1b/GM1 and GQ1b/GD1a. Gangliosides along with other components as cholesterol are known to form lipid rafts, in which the carbohydrate portions of two different gangliosides may form a new conformational epitope. Within the rafts, gangliosides are considered to interact with important receptors or signal transducers. The antibodies against ganglioside complexes may therefore directly cause nerve conduction failure and severe disability in GBS. More study is needed to elucidate the roles of the antibodies against ganglioside complexes.     

Campylobacter sialyltransferase gene polymorphism directs clinical features of Guillain-Barré syndrome

Progress has been made in Guillain-Barré syndrome, a post-infectious autoimmune neuropathy, especially on identifying Campylobacter jejuni genes responsible for the development and determinant of clinical features. C. jejuni strains carrying a sialyltransferase gene (cst-II), which is essential for the biosynthesis of ganglioside-like lipo-oligosaccharides (LOSs), are associated with the development of Guillain-Barré syndrome. The C. jejuni sialyltransferase (Cst-II) consists of 291 amino acids, and the 51st determines its enzymatic activity. Strains with cst-II (Thr51) expressed GM1-like and GD1a-like LOS, whereas strains with cst-II (Asn51) expressed GT1a-like and GD1c-like LOS. Patients infected with the cst-II (Thr51) strains had anti-GM1 or anti-GD1a IgG antibodies, and showed limb weakness. Patients infected with the cst-II (Asn51) strains had anti-GQ1b IgG antibodies, and showed ophthalmoplegia and ataxia. The cst-II gene is responsible for the development of Guillain-Barré and Fisher syndromes, and the polymorphism (Thr/Asn51) determines which syndrome develops after C. jejuni enteritis.     

Prominent plasmacytosis following intravenous immunoglobulin correlates with clinical improvement in Guillain-Barré syndrome

Background

High doses of pooled polyclonal IgG are commonly used to treat numerous autoimmune diseases. Their mode of action nevertheless remains only partially explained. At the same time, until now, no early biological marker has been able to predict their efficacy.

Methodology/Principal Findings

In a first pilot retrospective analysis, we reviewed white blood cell counts and blood smears in consecutive patients with autoimmune disease (n = 202) and non-autoimmune disease (n = 104). Autoimmune patients received either intravenous immunoglobulin (IVIg, n = 103), plasma exchange (n = 78) or no specific treatment (n = 21). We then prospectively monitored consecutive autoimmune patients with IVIg injection (n = 67), or without any specific treatment (n = 10) using the same routine laboratory tests, as well as flow cytometry. Both retrospective and prospective analyses identified large plasma-cell mobilization exclusively in IVIg-treated autoimmune patients 7 days after initiation of treatment. The majority of IVIg-mobilized plasma cells were immature HLA-DR^high/CD138^low/CXCR4^low plasma cells expressing intracellular immunoglobulin G which were neither IVIg- nor human IgG-specific. Importantly, we found a strong negative correlation between the absolute number of IVIg-mobilized plasma cells and time to improve neurological function in both retrospective and prospective studies of Guillain-Barré syndrome (GBS), (r = −0.52, p = 0.0031, n = 30, r = −0.47, p = 0.0028, n = 40, respectively).

Conclusions/Significance

IVIg promotes immature plasma-cell mobilization in patients with GBS, chronic inflammatory demyelinating polyneuropathy, myasthenia gravis and inflammatory myopathy. Prominent day 7 plasma-cell mobilization is a favourable prognostic marker in patients with GBS receiving IVIg treatment.     

Campylobacter jejuni infection in patient with Guillain-Barré syndrome: a case report

The Guillain-Barré syndrome is an acute inflammatory polineuropathy; it's frequency is established at the level of 1,3 cases/ 100 000 persons/ year. The main etiological factors concerned with the GBS occurrence are: Campylobacter jejuni, cytomegalovirus, Epstein-Barre virus, Mycoplasma pneumoniae. The authors present a case of the 15 years old boy with the clinical features of acute motor axonal polineuropathy and confirmed C. jejuni infection. Identification of C. jejuni isolate was based on colony morphology on CCDA plate (OXOID), characteristic motility, catalase, oxidase, hippurate hydrolysis and acetate hydrolysis. The identity of C. jejuni was also confirmed by a specific PCR. According to the authors' knowledge this is the first case of a patient with GBS with confirmed C. jejuni infection reported from Poland.     

Fluctuation in excitability of nerve fibres — a model study

Summary In this paper a mathematical model for the fluctuation in excitability of nerve fibres is presented. The model is based on the concept of a threshold subject to noise-like variations. Emphasis is laid on the rate of fluctuation of these disturbances.     

Guillain-Barré syndrome: rehabilitation outcome and recent developments.

Guillain-Barré syndrome is the most common polyneuropathy causing major disability and respiratory failure. Respiratory complications are the main cause of death. Improved respiratory care and new treatment strategies such as plasmaphoresis and immunoglobulin have been shown to improve outcome. We studied the course and outcome of 37 patients with Guillain-Barré syndrome who were admitted to a rehabilitation and respiratory care facility over a 10-year period. There were 21 males and 16 females with a mean age of 62+/-3 years. Fourteen patients developed respiratory failure requiring endotracheal intubation and mechanical ventilation. The mean duration of mechanical ventilation was 38+/-10 days. All patients were successfully liberated from the ventilator. However, 83 percent of the patients were moderately to severely disabled at the time of discharge. Thirteen out of 37 (35 percent) developed long-term disability. None of the patients died over the period of follow-up. These results indicate that early recognition and treatment of respiratory complications in Guillain-Barré syndrome could reduce the morbidity and mortality of this condition.