The Experts below are selected from a list of 2403 Experts worldwide ranked by ideXlab platform
Nobuhiro Yuki - One of the best experts on this subject based on the ideXlab platform.
-
Polyclonal IgM and IgA block in vitro complement deposition mediated by anti-Ganglioside antibodies in autoimmune neuropathies
International immunopharmacology, 2016Co-Authors: Makoto Sudo, Yoshiki Yamaguchi, Peter J. Späth, Kazuki Miyaji, Kana Morita-matsumoto, Nobuhiro YukiAbstract:Intravenous immunoglobulin (IVIG), consisting of IgG, is the first-line treatment for Guillain-Barre syndrome and multifocal motor neuropathy. IgG, but neither IgM nor IgA, has been demonstrated in vitro to inhibit complement deposition mediated by anti-Ganglioside autoantibodies in sera from patients with both conditions. The objective of this study is to investigate the in vitro effectiveness of IgM and IgA in inhibiting complement deposition to Ganglioside/anti-Ganglioside Antibody complexes. Serum samples were obtained from patients with multifocal motor neuropathy associated with anti-GM1 IgM antibodies, Guillain-Barre syndrome associated with anti-GM1 IgG antibodies and Miller Fisher syndrome associated with anti-GQ1b IgG antibodies. Inhibition of complement deposition using different immunoglobulin preparations was measured by enzyme-linked immunosorbent assay. IgM/A-enriched IVIG and immunoglobulin isotypes (polyclonal IgM and IgA) showed higher potential in inhibiting complement deposition than standard IVIG. Although the safety concerns about the use of IgM and IgA for an immunotherapy still remain, IgM and IgA may serve as an alternative immunotherapy in those anti-Ganglioside Antibody-mediated neuropathies.
-
different ivig glycoforms affect in vitro inhibition of anti Ganglioside Antibody mediated complement deposition
PLOS ONE, 2014Co-Authors: Makoto Sudo, Yoshiki Yamaguchi, Benjamin K. Ong, Nortina Shahrizaila, Peter J. Späth, Kana Matsumotomorita, Nobuhiro YukiAbstract:Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain–Barre syndrome and multifocal motor neuropathy, which are caused by anti-Ganglioside Antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in Antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of Antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain–Barre syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-Ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoAntibody binding to Ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.
-
Different IVIG Glycoforms Affect In Vitro Inhibition of Anti-Ganglioside Antibody-Mediated Complement Deposition
2014Co-Authors: Makoto Sudo, Yoshiki Yamaguchi, Peter J. Späth, Kana Matsumoto-morita, Benjamin K. Ong, Nortina Shahrizaila, Nobuhiro YukiAbstract:Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain–Barre ́ syndrome and multifocal motor neuropathy, which are caused by anti-Ganglioside Antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in Antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of Antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain–Barre ́ syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-Ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoAntibody binding to Ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependen
-
Different IVIG Glycoforms Affect In Vitro Inhibition of Anti-Ganglioside Antibody-Mediated Complement Deposition
2014Co-Authors: Makoto Sudo, Yoshiki Yamaguchi, Kana Matsumoto-morita, Benjamin K. Ong, Nortina Shahrizaila, Peter J. Späth, Nobuhiro YukiAbstract:Intravenous immunoglobulin (IVIG) is the first line treatment for Guillain–Barré syndrome and multifocal motor neuropathy, which are caused by anti-Ganglioside Antibody-mediated complement-dependent cytotoxicity. IVIG has many potential mechanisms of action, and sialylation of the IgG Fc portion reportedly has an anti-inflammatory effect in Antibody-dependent cell-mediated cytotoxicity models. We investigated the effects of different IVIG glycoforms on the inhibition of Antibody-mediated complement-dependent cytotoxicity. Deglycosylated, degalactosylated, galactosylated and sialylated IgG were prepared from IVIG following treatment with glycosidases and glycosyltransferases. Sera from patients with Guillain–Barré syndrome, Miller Fisher syndrome and multifocal motor neuropathy associated with anti-Ganglioside antibodies were used. Inhibition of complement deposition subsequent to IgG or IgM autoAntibody binding to Ganglioside, GM1 or GQ1b was assessed on microtiter plates. Sialylated and galactosylated IVIGs more effectively inhibited C3 deposition than original IVIG or enzyme-treated IVIGs (agalactosylated and deglycosylated IVIGs). Therefore, sialylated and galactosylated IVIGs may be more effective than conventional IVIG in the treatment of complement-dependent autoimmune diseases.
-
Nodo-paranodopathy: beyond the demyelinating and axonal classification in anti-Ganglioside Antibody-mediated neuropathies.
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology, 2013Co-Authors: Antonino Uncini, Keiichiro Susuki, Nobuhiro YukiAbstract:In some anti-Ganglioside Antibody-mediated neuropathies, human and experimental data suggest a common pathogenic mechanism of dysfunction/disruption at the node of Ranvier resulting in a pathophysiologic continuum from transitory nerve conduction failure to axonal degeneration. The traditional classification of polyneuropathies into demyelinating or axonal may generate some confusion in the electrophysiological diagnosis of Guillain-Barre syndrome subtypes associated with anti-Ganglioside antibodies. The axonal forms show, besides axonal degeneration, promptly reversible nerve conduction failure. This may be interpreted, by a single electrophysiological study, as demyelinating conduction block or distal axonal degeneration leading to errors in classification and in establishing prognosis. Moreover the term axonal may be misleading as it is commonly associated to axonal degeneration and not to a transitory, promptly reversible, dysfunction of the excitable axolemma. To focus on the site of nerve injury and overcome the classification difficulties, we propose the new category of nodo-paranodopathy which seems appropriate to various acute and chronic neuropathies associated with anti-Ganglioside antibodies and we think better systematizes the neuropathies characterized by an autoimmune attack targeting the nodal region.
Hugh J. Willison - One of the best experts on this subject based on the ideXlab platform.
-
Anti-Ganglioside antibodies are removed from circulation in mice by neuronal endocytosis
Brain, 2016Co-Authors: Madeleine E Cunningham, Susan K Halstead, J. A. Barrie, Rhona Mcgonigal, Gavin R Meehan, Denggao Yao, Hugh J. WillisonAbstract:See van Doorn and Jacobs (doi:[10.1093/brain/aww078][1]) for a scientific commentary on this article. In axonal forms of Guillain-Barre syndrome, anti-Ganglioside antibodies bind Gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-Ganglioside antibodies from the cell surface so rapidly that Antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-Ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating Antibody levels. Remarkably, systemically delivered anti-Ganglioside Antibody in mice was so avidly cleared from the circulation by endocytosis at Ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-Ganglioside Antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-Ganglioside antibodies, and potentially other Ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system. * Abbreviations : AGAbs = : anti-Ganglioside antibodies BoNT/A = : Botulinum toxin A NMJ = : neuromuscular junction [1]: /lookup/doi/10.1093/brain/aww078
-
Anti-Ganglioside antibodies are removed from circulation in mice by neuronal endocytosis.
Brain : a journal of neurology, 2016Co-Authors: Madeleine E Cunningham, Susan K Halstead, Rhona Mcgonigal, Gavin R Meehan, Jennifer A Barrie, Denggao Yao, Hugh J. WillisonAbstract:SEE VAN DOORN AND JACOBS DOI101093/BRAIN/AWW078 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE : In axonal forms of Guillain-Barré syndrome, anti-Ganglioside antibodies bind Gangliosides on nerve surfaces, thereby causing injury through complement activation and immune cell recruitment. Why some nerve regions are more vulnerable than others is unknown. One reason may be that neuronal membranes with high endocytic activity, including nerve terminals involved in neurotransmitter recycling, are able to endocytose anti-Ganglioside antibodies from the cell surface so rapidly that Antibody-mediated injury is attenuated. Herein we investigated whether endocytic clearance of anti-Ganglioside antibodies by nerve terminals might also be of sufficient magnitude to deplete circulating Antibody levels. Remarkably, systemically delivered anti-Ganglioside Antibody in mice was so avidly cleared from the circulation by endocytosis at Ganglioside-expressing plasma membranes that it was rapidly rendered undetectable in serum. A major component of the clearance occurred at motor nerve terminals of neuromuscular junctions, from where anti-Ganglioside Antibody was retrogradely transported to the motor neuron cell body in the spinal cord, recycled to the plasma membrane, and secreted into the surrounding spinal cord. Uptake at the neuromuscular junction represents a major unexpected pathway by which pathogenic anti-Ganglioside antibodies, and potentially other Ganglioside binding proteins, are cleared from the systemic circulation and also covertly delivered to the central nervous system.
-
anti Ganglioside Antibody internalization attenuates motor nerve terminal injury in a mouse model of acute motor axonal neuropathy
Journal of Clinical Investigation, 2012Co-Authors: Simon N Fewou, Angie Rupp, Kay N. Greenshields, Jaap J Plomp, Lauren E Nickolay, Kathryn Carrick, John D Pediani, Hugh J. WillisonAbstract:In the Guillain-Barre syndrome subform acute motor axonal neuropathy (AMAN), Campylobacter jejuni enteritis triggers the production of anti-Ganglioside Abs (AGAbs), leading to immune-mediated injury of distal motor nerves. An important question has been whether injury to the presynaptic neuron at the neuromuscular junction is a major factor in AMAN. Although disease modeling in mice exposed to AGAbs indicates that complement-mediated necrosis occurs extensively in the presynaptic axons, evidence in humans is more limited, in comparison to the extensive injury seen at nodes of Ranvier. We considered that rapid AGAb uptake at the motor nerve terminal membrane might attenuate complement-mediated injury. We found that PC12 rat neuronal cells rapidly internalized AGAb, which were trafficked to recycling endosomes and lysosomes. Consequently, complement-mediated cytotoxicity was attenuated. Importantly, we observed the same AGAb endocytosis and protection from cytotoxicity in live mouse nerve terminals. AGAb uptake was attenuated following membrane cholesterol depletion in vitro and ex vivo, indicating that this process may be dependent upon cholesterol-enriched microdomains. In contrast, we observed minimal AGAb uptake at nodes of Ranvier, and this structure thus remained vulnerable to complement-mediated injury. These results indicate that differential endocytic processing of AGAbs by different neuronal and glial membranes might be an important modulator of site-specific injury in acute AGAb-mediated Guillain-Barre syndrome subforms and their chronic counterparts.
-
Motor nerve terminal destruction and regeneration following anti-Ganglioside Antibody and complement-mediated injury: an in and ex vivo imaging study in the mouse.
Experimental neurology, 2011Co-Authors: Angie Rupp, Susan K Halstead, Ian Morrison, J. A. Barrie, Kate Townson, Kay N. Greenshields, Hugh J. WillisonAbstract:Both the neural and glial components of the neuromuscular junction (NMJ) have been identified as potential sites for anti-Ganglioside Antibody (Ab) binding and complement-mediated injury in murine models for the human peripheral nerve disorder Guillain-Barre syndrome (GBS). Some patients suffering from the acute motor axonal neuropathy (AMAN) forms of GBS recover very rapidly from paralysis; it has been proposed that in these cases the injury was restricted to the distal motor axons and nerve terminals (NTs) which are able to regenerate over a very short time-frame. To test this hypothesis, the ventral neck muscles of mice (n=45) expressing cytosolic fluorescent proteins in their axons (CFP) and Schwann cells (GFP) were subjected to a single topical application of anti-Ganglioside Ab followed by a source of complement. Group A (n=15) received Ab that selectively bound to the NTs, group B (n=15) received Abs that bound both to the NTs and the perisynaptic Schwann cells (pSCs) and group C (control animals; n=15) only received complement. Evolution of the injury was documented by in vivo imaging, and following euthanasia the muscles were reimaged ex vivo both quantitatively and qualitatively, either immediately, or after 1, 2, 3 or 5 days of regeneration (each n=3 per group). Within 15 minutes of complement application, a rapid loss of CFP overlying the NMJ could be seen; in group A, the GFP signal remained unchanged, whereas in group B the GFP signal was also lost. In group C no changes to either CFP or GFP were observed. At 24 h, 6% of the superficial NMJs in group A and 12% of the NMJs in group B exhibited CFP. In both groups, CFP returned within the next five days (group A: 93.5%, group B: 94%; p=0.739), with the recovery of CFP being preceded by a return of GFP-positive cells overlying the NMJ in group B. Auxiliary investigations revealed that the loss of CFP at the NMJ correlated with a loss of NT neurofilament immuno-reactivity and a return of CFP at the NMJ was accompanied by a return of neurofilament. In ultrastructural investigations, injured NTs were electron lucent and exhibited damaged mitochondria, a loss of filaments and a loss of synaptic vesicles. The examination of muscles after five days of regeneration revealed physiological NT-profiles. The results described above indicate that following a single anti-Ganglioside Ab-mediated and complement-mediated attack, independent of whether there are healthy and mature perisynaptic Schwann cells overlying the NMJ, the murine NT is capable of recovering both its architectural and axolemmal integrity very rapidly. This data supports the notion that an equivalent mechanism may account for the rapid recovery seen in some clinical cases of AMAN.
-
Glycosphingolipid depletion in PC12 cells using iminosugars protects neuronal membranes from anti-Ganglioside Antibody mediated injury.
Journal of neuroimmunology, 2008Co-Authors: Kate Townson, Hugh J. Willison, Kay N. Greenshields, Anneliese O. Speak, Carl S. Goodyear, Frances M. PlattAbstract:Autoimmune neuropathies are frequently associated with pathogenic anti-Ganglioside antibodies targeting Ganglioside-rich neuronal and glial membranes. The extent of injury is determined by the concentration of membrane Ganglioside and thus reduction might be expected to attenuate disease. In this study, we suppressed Ganglioside biosynthesis in PC12 cells with the glucosylceramide synthase inhibitor, N-butyldeoxynojirimycin and observed reduced plasma membrane Antibody binding and a major neuroprotective effect in complement-mediated lysis assays. These data demonstrate that iminosugar inhibitors, currently used to treat type 1 Gaucher disease, are also of potential value for depleting antigen and thereby suppressing tissue injury in anti-Ganglioside Antibody-associated neuropathy.
Takao Mitsui - One of the best experts on this subject based on the ideXlab platform.
-
Dissociation between titer of anti-Ganglioside Antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.
Journal of the neurological sciences, 2003Co-Authors: Nami Inoue, Yasushi Oshima, Hiide Yoshino, Makoto Kunishige, Atsuko Asano, Toshio Matsumoto, Sumiko Yoshida, Yoshiaki Ohnishi, Yasuhiro Kuroda, Takao MitsuiAbstract:Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barré syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-Ganglioside Antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-Ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.
-
Dissociation between titer of anti-Ganglioside Antibody and severity of symptoms in a case of Guillain-Barré syndrome with treatment-related fluctuation.
Journal of the Neurological Sciences, 2003Co-Authors: Nami Inoue, Yasushi Oshima, Hiide Yoshino, Makoto Kunishige, Atsuko Asano, Toshio Matsumoto, Sumiko Yoshida, Yoshiaki Ohnishi, Yasuhiro Kuroda, Takao MitsuiAbstract:Since plasma exchange (PE) and intravenous immunoglobulin (i.v.Ig) have been widely used in treatment for Guillain-Barre syndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal-dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by i.v.Ig, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-Ganglioside Antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-Ganglioside antibodies but presumably to the transient beneficial effects of DFPP/i.v.Ig and the outlasting inflammatory response in peripheral nerves.
-
Short communication Dissociation between titer of anti-Ganglioside Antibody and severity of symptoms in a case of Guillain-Barresyndrome with treatment-related fluctuation
2003Co-Authors: Nami Inoue, Yasushi Oshima, Hiide Yoshino, Makoto Kunishige, Atsuko Asano, Toshio Matsumoto, Sumiko Yoshida, Yoshiaki Ohnishi, Yasuhiro Kuroda, Takao MitsuiAbstract:Since plasma exchange (PE) and intravenous immunoglobulin (IVIg) have been widely used in treatment for Guillain-Barresyndrome (GBS), early relapse and treatment-related fluctuation have been a potential problem, but little is known about the mechanism of relapse and fluctuation. We describe a patient who had GBS with treatment-related fluctuation. A 37-year-old Japanese man exhibited acute distal- dominant weakness in upper limbs after upper respiratory infection. His cranial nerve system was normal and muscle weakness was limited to upper limbs. Anti-GT1a IgG was strongly positive and anti-GQ1b IgG was also detected in his serum. Muscle weakness responded well to double-filtration plasmapheresis (DFPP) followed by IVIg, but relapsed 45 days after the initial treatment. Although repeated treatments were effective, the patient showed additional minor deterioration twice. Motor nerve conduction velocities (MCVs) corresponded to the muscle weakness, but elevated level of cerebrospinal fluid (CSF) protein remained and anti-Ganglioside Antibody titers steadily decreased throughout the clinical course. These findings indicate that the clinical fluctuation was not due to changes in the production of anti-Ganglioside antibodies but presumably to the transient beneficial effects of DFPP/IVIg and the outlasting inflammatory response in peripheral nerves. D 2003 Elsevier Science B.V. All rights reserved.
-
central motor conduction in patients with anti Ganglioside Antibody associated neuropathy syndromes and hyperreflexia
Journal of Neurology Neurosurgery and Psychiatry, 2002Co-Authors: Yasushi Oshima, Takao Mitsui, Hiide Yoshino, I Endo, Makoto Kunishige, Atsuko Asano, Toshio MatsumotoAbstract:Objectives: Several serum antibodies against Gangliosides are diagnostically important, particularly in Guillain-Barre syndrome (GBS), Miller Fisher syndrome (MFS), and multifocal motor neuropathy (MMN). Although hyperreflexia is an atypical symptom in these disorders, it has been found in some patients with GBS, MFS, and MMN. The aim of the study was to determine whether hyperreflexia corresponds to corticospinal tract dysfunction in these patients. Methods: The study examined central and peripheral motor conduction in patients with hyperreflexia who exhibited acute paralysis (group 1, n=5), acute ataxia and ophthalmoplegia (group 2, n=7), or chronic paralysis with conduction block (group 3, n=2). The clinical symptoms are similar to those in patients with GBS, MFS, and MMN, respectively, and serum anti-Ganglioside antibodies were found to be positive in all patients. Using magnetic and electrical stimulation techniques, central and peripheral motor conduction were compared in patients in groups 1, 2, and 3 and patients with GBS (n=7), MFS (n=8), and MMN (n=6). Results: Central motor conduction times (CMCTs) in patients in groups 1, 2, and 3 were significantly delayed compared with those in patients with GBS, MFS, and MMN (p<0.01, p<0.05, p<0.05, respectively), and the delayed CMCTs significantly improved in the recovery periods (p<0.01, p<0.01, p<0.05, respectively). However, motor conduction velocity, compound muscle action potential, and F wave conduction velocity were not significantly different between the patients. Conclusion: These findings indicate that corticospinal tract is functionally involved in patients with anti-Ganglioside Antibody associated neuropathy syndromes and hyperreflexia
-
Central motor conduction in patients with anti-Ganglioside Antibody associated neuropathy syndromes and hyperreflexia
Journal of neurology neurosurgery and psychiatry, 2002Co-Authors: Yasushi Oshima, Takao Mitsui, Hiide Yoshino, Makoto Kunishige, Atsuko Asano, Endo I, Toshio MatsumotoAbstract:Objectives: Several serum antibodies against Gangliosides are diagnostically important, particularly in Guillain-Barre syndrome (GBS), Miller Fisher syndrome (MFS), and multifocal motor neuropathy (MMN). Although hyperreflexia is an atypical symptom in these disorders, it has been found in some patients with GBS, MFS, and MMN. The aim of the study was to determine whether hyperreflexia corresponds to corticospinal tract dysfunction in these patients. Methods: The study examined central and peripheral motor conduction in patients with hyperreflexia who exhibited acute paralysis (group 1, n=5), acute ataxia and ophthalmoplegia (group 2, n=7), or chronic paralysis with conduction block (group 3, n=2). The clinical symptoms are similar to those in patients with GBS, MFS, and MMN, respectively, and serum anti-Ganglioside antibodies were found to be positive in all patients. Using magnetic and electrical stimulation techniques, central and peripheral motor conduction were compared in patients in groups 1, 2, and 3 and patients with GBS (n=7), MFS (n=8), and MMN (n=6). Results: Central motor conduction times (CMCTs) in patients in groups 1, 2, and 3 were significantly delayed compared with those in patients with GBS, MFS, and MMN (p
Koichi Hirata - One of the best experts on this subject based on the ideXlab platform.
-
dysfunction of nodes of ranvier a mechanism for anti Ganglioside Antibody mediated neuropathies
Experimental Neurology, 2012Co-Authors: Keiichiro Susuki, Gang Zhang, Nobuhiro Yuki, Koichi Hirata, Dorothy P Schafer, Kei Funakoshi, Matthew N RasbandAbstract: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.
-
Isolated abducens nerve palsy as a regional variant of Guillain–Barré syndrome
Journal of the Neurological Sciences, 2006Co-Authors: Muneto Tatsumoto, Koichi Hirata, Masaaki Odaka, Nobuhiro YukiAbstract:Abstract The authors reviewed clinical profiles and laboratory findings for 100 cases of abducens nerve paresis without impairment of the other cranial nerves, limb weakness, and ataxia throughout the clinical course. Review of the medical records of 9300 patients referred to our neuoroimmunological laboratory for serum anti-Ganglioside Antibody testing. Information was obtained from each primary physician on symptoms of preceding infection; initial symptoms; neurological signs during the illness; the clinical course; treatment provided; and outcome. Isolated abducens nerve paresis was present in 100 patients and bilateral paresis in 29. Tentative diagnoses made by the primary physicians on request of anti-Ganglioside Antibody testing were abducens nerve palsy (n = 68), Fisher syndrome (n = 14), acute ophthalmoparesis without ataxia (n = 14). Symptoms of infection anteceded in 63. Tendon reflexes were absent or decreased in 27. Distal paresthesias were experienced by seven. Serum anti-GQ1b Antibody was positive in 25. These findings suggest that some cases of isolated abducens nerve palsy can be categorized as a regional variant of Guillain–Barre syndrome or mild form of Fisher syndrome.
-
Isolated abducens nerve palsy as a regional variant of Guillain-Barré syndrome.
Journal of the neurological sciences, 2006Co-Authors: Muneto Tatsumoto, Koichi Hirata, Masaaki Odaka, Nobuhiro YukiAbstract:The authors reviewed clinical profiles and laboratory findings for 100 cases of abducens nerve paresis without impairment of the other cranial nerves, limb weakness, and ataxia throughout the clinical course. Review of the medical records of 9300 patients referred to our neuoroimmunological laboratory for serum anti-Ganglioside Antibody testing. Information was obtained from each primary physician on symptoms of preceding infection; initial symptoms; neurological signs during the illness; the clinical course; treatment provided; and outcome. Isolated abducens nerve paresis was present in 100 patients and bilateral paresis in 29. Tentative diagnoses made by the primary physicians on request of anti-Ganglioside Antibody testing were abducens nerve palsy (n = 68), Fisher syndrome (n = 14), acute ophthalmoparesis without ataxia (n = 14). Symptoms of infection anteceded in 63. Tendon reflexes were absent or decreased in 27. Distal paresthesias were experienced by seven. Serum anti-GQ1b Antibody was positive in 25. These findings suggest that some cases of isolated abducens nerve palsy can be categorized as a regional variant of Guillain-Barré syndrome or mild form of Fisher syndrome.
-
Longitudinal changes of anti-Ganglioside antibodies before and after Guillain-Barré syndrome onset subsequent to Campylobacter jejuni enteritis.
Journal of the neurological sciences, 2003Co-Authors: Masaaki Odaka, Michiaki Koga, Nobuhiro Yuki, Keiichiro Susuki, Koichi HirataAbstract: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.
-
Longitudinal changes of anti-Ganglioside antibodies before and after Guillain-Barré syndrome onset subsequent to Campylobacter jejuni enteritis.
Journal of the Neurological Sciences, 2003Co-Authors: Masaaki Odaka, Michiaki Koga, Nobuhiro Yuki, Keiichiro Susuki, Koichi HirataAbstract:Anti-Ganglioside antibodies frequently are present in sera from patients with Guillain-Barre 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.
Kazim A. Sheikh - One of the best experts on this subject based on the ideXlab platform.
-
Fcc Receptor-Mediated Inflammation Inhibits Axon Regeneration
2016Co-Authors: Gang Zhang, Tong Gao, Nataliia Bogdanova, Julia J. Song, Mark S. Cragg, Martin J. Glennie, Kazim A. SheikhAbstract:Anti-glycan/Ganglioside antibodies are the most common immune effectors found in patients with Guillain-Barre ́ Syndrome, which is a peripheral autoimmune neuropathy. We previously reported that disease-relevant anti-glycan autoantibodies inhibited axon regeneration, which echo the clinical association of these antibodies and poor recovery in Guillain-Barré Syndrome. However, the specific molecular and cellular elements involved in this Antibody-mediated inhibition of axon regeneration are not previously defined. This study examined the role of Fcc receptors and macrophages in the Antibody-mediated inhibition of axon regeneration. A well characterized Antibody passive transfer sciatic nerve crush and transplant models were used to study the anti-Ganglioside Antibody-mediated inhibition of axon regeneration in wild type and various mutant and transgenic mice with altered expression of specific Fcc receptors and macrophage/microglia populations. Outcome measures included behavior, electrophysiology, morphometry, immunocytochemistry, quantitative real-time PCR, and western blotting. We demonstrate that the presence of autoantibodies, directed against neuronal/axonal cell surface Gangliosides, in the injured mammalian peripheral nerves switch the proregenerative inflammatory environment to growth inhibitory milieu by engaging specific activating Fcc receptors on recruited monocyte-derived macrophages to cause severe inhibition of axon regeneration. Our data demonstrate that the Antibody orchestrated Fcc receptor-mediated switch in inflammation is one mechanism underlying inhibition of axon regeneration. These findings have clinical implications fo
-
Sialylated intravenous immunoglobulin suppress anti-Ganglioside Antibody mediated nerve injury.
Experimental neurology, 2016Co-Authors: Gang Zhang, Cynthia A. Massaad, Tong Gao, Laila Pillai, Nataliia Bogdanova, Sameera Ghauri, Kazim A. SheikhAbstract:The precise mechanisms underlying the efficacy of intravenous immunoglobulin (IVIg) in autoimmune neurological disorders including Guillain-Barre syndrome (GBS) are not known. Anti-Ganglioside antibodies have been reported to be pathogenic in some variants of GBS, and we have developed passive transfer animal models to study anti-Ganglioside Antibody mediated-endoneurial inflammation and associated neuropathological effects and to evaluate the efficacy of new therapeutic approaches. Some studies indicate that IVIg's anti-inflammatory activity resides in a minor sialylated IVIg (sIVIg) fractions and is dependent on an innate Th2 response via binding to a specific ICAM3-grabbing nonintegrin related 1 receptor (SIGN-R1). Therefore the efficacy of IVIg, IVIg fractions with various IgG Fc sialylation status, and the involvement of Th2 pathway were examined in one of our animal model of Antibody-mediated inhibition of axonal regeneration. We demonstrate that both IVIg and sIVIg ameliorated anti-glycan Antibody mediated-pathological effect, whereas, the unsialylated fractions of IVIg were not beneficial in our model. Tenfold lower doses of sIVIg compared to whole IVIg provided equivalent efficacy in our studies. Moreover, we found that whole IVIg and sIVIg significantly upregulates the gene expression of IL-33, which itself can provide protection from Antibody-mediated nerve injury in our model. Our results support that the SIGN-R1-Th2 pathway is involved in the anti-inflammatory effects of IVIg on endoneurium in our model and elements of this pathway including IL-33 can provide novel therapeutics in inflammatory neuropathies.
-
fluorescently tagged anti Ganglioside Antibody selectively identifies peripheral nerve in living animals
Scientific Reports, 2015Co-Authors: Cynthia A. Massaad, Gang Zhang, Laila Pillai, Ali Azhdarinia, Weiqiang Liu, Kazim A. SheikhAbstract:Selective in vivo delivery of cargo to peripheral nervous system (PNS) has broad clinical and preclinical applications. An important applicability of this approach is systemic delivery of fluorescently conjugated ligands that selectively label PNS, which could allow visualization of peripheral nerves during any surgery. We examine the use of an anti-Ganglioside monoclonal Antibody (mAb) as selective neuronal delivery vector for surgical imaging of peripheral nerves. Systemic delivery of an anti-Ganglioside mAb was used for selective intraneuronal/axonal delivery of fluorescent agents to visualize nerves by surgical imaging in living mice. In this study, we show that intact motor, sensory, and autonomic nerve fibers/paths are distinctly labeled following a single nanomolar systemic injection of fluorescently labeled anti-Ganglioside mAb. Tissue biodistribution studies with radiolabeled mAb were used to validate neuronal uptake of fluorescently labeled mAb. Implications of this proof of concept study are that fluorescent conjugates of anti-Ganglioside mAbs are valuable delivery vectors to visualize nerves during surgery to avoid nerve injury and monitor nerve degeneration and regeneration after injury. These findings support that antibodies, and their derivatives/fragments, can be used as selective neuronal delivery vector for transport of various cargos to PNS in preclinical and clinical settings.
-
erythropoietin enhances nerve repair in anti Ganglioside Antibody mediated models of immune neuropathy
PLOS ONE, 2011Co-Authors: Gang Zhang, Nataliia Bogdanova, Helmar C. Lehmann, Jiangyang Zhang, Kazim A. SheikhAbstract:Guillain-Barre syndrome (GBS) is a monophasic immune neuropathic disorder in which a significant proportion of patients have incomplete recovery. The patients with incomplete recovery almost always have some degree of failure of axon regeneration and target reinnervation. Anti-Ganglioside antibodies (Abs) are the most commonly recognized autoimmune markers in all forms of GBS and specific Abs are associated with the slow/poor recovery. We recently demonstrated that specific anti-Ganglioside Abs inhibit axonal regeneration and nerve repair in preclinical models by activation of small GTPase RhoA and its downstream effectors. The objective of this study was to determine whether erythropoietin (EPO), a pleiotropic cytokine with neuroprotective and neurotrophic properties, enhances nerve regeneration in preclinical cell culture and animal models of autoimmune neuropathy/nerve repair generated with monoclonal and patient derived Abs. Primary neuronal cultures and a standardized sciatic crush nerve model were used to assess the efficacy of EPO in reversing inhibitory effects of anti-Ganglioside Abs on nerve repair. We found that EPO completely reversed the inhibitory effects of anti-Ganglioside Abs on axon regeneration in cell culture models and significantly improved nerve regeneration/repair in an animal model. Moreover, EPO-induced proregenerative effects in nerve cells are through EPO receptors and Janus kinase 2/Signal transducer and activator of transcription 5 pathway and not via early direct modulation of small GTPase RhoA. These preclinical studies indicate that EPO is a viable candidate drug to develop further for neuroprotection and enhancing nerve repair in patients with GBS.
-
Anti-Ganglioside Antibody-mediated activation of RhoA induces inhibition of neurite outgrowth
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2011Co-Authors: Gang Zhang, Ronald L. Schnaar, Pablo H H Lopez, Nataliia Bogdanova, Helmar C. Lehmann, Sowmia Manoharan, Mohammedali Hashmi, Sangwoo Shim, Guo Li Ming, Kazim A. SheikhAbstract:Anti-Ganglioside antibodies (Abs) are strongly associated with axonal forms of Guillain Barre syndrome (GBS). Some studies indicate that these Abs, including those with GD1a reactivity, are associated with poor prognosis and/or incomplete recovery. We recently demonstrated that a disease-relevant anti-Ganglioside Ab with GD1a reactivity inhibits axon regeneration after PNS injury in an animal model (Lehmann et al., 2007). An implication of these findings is that anti-GD1a Abs can mediate inhibition of axon regeneration and limit recovery in some patients with GBS. The downstream inhibitory intracellular signaling that mediates anti-Ganglioside Ab-induced axon inhibition remains unclear. In the current study, we show that disease-relevant and GBS patient's anti-Ganglioside Abs can inhibit neurite outgrowth in dissociated primary neuronal cultures. Activation of small GTPase RhoA and its key downstream effector Rho kinase (ROCK) are critical mediators of growth cone and neurite outgrowth inhibition. Therefore, we examined the role of these intracellular signaling molecules in our primary neuronal cultures by molecular and pharmacologic approaches. Our results show that the Ab-mediated inhibition of neurite outgrowth involves the activation of RhoA and ROCK pathway and this activation is through the engagement of specific cell-surface Gangliosides by Abs. In summary, these studies directly link patient autoantibodies to an intracellular inhibitory signaling pathway involved in anti-Ganglioside Ab-mediated inhibition of neurite outgrowth.
