Acute conduction block in vitro following exposure to antiganglioside sera

Arasaki, Keisuke; Kusunoki, Susumu; Kudo, Norio; Kanazawa, Ichiro

doi:10.1002/mus.880160603

Cited by 104 publications

(30 citation statements)

References 23 publications

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“…With respect to the antibody induction phase of the illness, it is clearly established that anti-GM1 antibodies can arise through molecular mimicry with structurally homologous Campylobacter jejuni lipooligosaccharides (LOS) (15)(16)(17)(18). In contrast, examination of the effector pathways through which anti-GM1 antibodies selectively bind to and induce injury in motor nerve membranes, while avoiding damage to other neural and non-neural plasma membranes containing abundant GM1, is confounded by inconsistent and often counterintuitive data (9,(19)(20)(21)(22). In particular, the sensitivity or resistance of the membrane toward undergoing anti-GM1 antibody-mediated injury cannot be fully explained by the presence and density of plasma membrane GM1.…”

Section: Introductionmentioning

confidence: 99%

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice

Greenshields¹,

Halstead²,

Zitman³

et al. 2009

J. Clin. Invest.

104

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Anti-GM1 ganglioside autoantibodies are used as diagnostic markers for motor axonal peripheral neuropathies and are believed to be the primary mediators of such diseases. However, their ability to bind and exert pathogenic effects at neuronal membranes is highly inconsistent. Using human and mouse monoclonal anti-GM1 antibodies to probe the GM1-rich motor nerve terminal membrane in mice, we here show that the antigenic oligosaccharide of GM1 in the live plasma membrane is cryptic, hidden on surface domains that become buried for a proportion of anti-GM1 antibodies due to a masking effect of neighboring gangliosides. The cryptic GM1 binding domain was exposed by sialidase treatment that liberated sialic acid from masking gangliosides including GD1a or by disruption of the live membrane by freezing or fixation. This cryptic behavior was also recapitulated in solid-phase immunoassays. These data show that certain anti-GM1 antibodies exert potent complement activation-mediated neuropathogenic effects, including morphological damage at living terminal motor axons, leading to a block of synaptic transmission. This occurred only when GM1 was topologically available for antibody binding, but not when GM1 was cryptic. This revised understanding of the complexities in ganglioside membrane topology provides a mechanistic account for wide variations in the neuropathic potential of anti-GM1 antibodies.

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Section: Introductionmentioning

confidence: 99%

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice

Greenshields¹,

Halstead²,

Zitman³

et al. 2009

J. Clin. Invest.

104

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“…We show that the antibody binds to a wide range of peripheral nerve structures and induces electrophysiological abnormalities in mouse nerve compatible with its putative pathophysiological effects on the human peripheral nervous system (PNS). Previous animal studies using antiganglioside antibodies to induce experimental neuropathy using whole sera or partially purified sera (23)(24)(25)(26)(27)(28)(29)(30)(31)(32) have also shown immunopathogenic effects. These data lend great support to the view that antiganglioside antibodies have the capacity to induce autoimmune neurological disease.…”

Section: Introductionmentioning

confidence: 99%

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

Willison

O’Hanlon²,

Paterson³

et al. 1996

J. Clin. Invest.

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IgM paraproteins associated with autoimmune peripheral neuropathy and anti-Pr cold agglutinins react with sialic acid epitopes present on disialylated gangliosides including GD1b, GT1b, GQ1b, and GD3. A causal relationship between the paraprotein and the neuropathy has never been proven experimentally. From peripheral blood B cells of an affected patient, we have cloned a human hybridoma secreting an antidisialosyl IgM mAb, termed Ha1, that shows identical structural and functional characteristics to its serum counterpart. Variable region analysis shows Ha1 is encoded by the same V H 1 family heavy chain gene, V1-18, as the only other known anti-Pr antibody sequence and is somatically mutated, suggesting that is arose in vivo in response to antigenic stimulation. In the rodent peripheral nervous system, Ha1 immunolocalizes to dorsal root ganglia, motor nerve terminals, muscle spindles, myelinated axons, and nodes of Ranvier. After intraperitoneal injection of affinity-purified antibody into mice for 10 d, electrophysiological recordings from the phrenic nerve-hemidiaphragm preparation demonstrated impairment of nerve excitability and a reduction in quantal release of neurotransmitter. These data unequivocally establish that an antidisialosyl antibody can exert pathophysiological effects on the peripheral nervous system and strongly support the view that the antibody contributes to the associated human disease. ( J. Clin. Invest. 1996. 97:1155-1164.)

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“…Recently, it has been shown that high titers of anti-GM l antisera from rabbits immunized with GM1ganglioside induce impairment of action potential with an accompanying decrease in Na+currents and an increase in K+currents in rat myelinated nerve fibers (6). However, there have been controversial results on the effect of anti-GMl antibody on nerve fibers and neurons (7)(8)(9). This may be partly due to the different methods which each study used.…”

Section: Introductionmentioning

confidence: 99%

The Sera from GM1 Ganglioside Antibody Positive Patients with Guillain-Barre Syndrome or Chronic Inflammatory Demyelinating Polyneuropathy Blocks Na+ Currents in Rat Single Myelinated Nerve Fibers.

et al. 2000

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Objective To determine the possible role of anti-GMl ganglioside antisera from patients with Gullain-Barre syndrome (GBS) or chronic inflammatory demyelinating polyneuropathy (CIDP) in the development of nerve dysfunction.Methods The effect of the anti-GMl antibody positive antisera obtained from 4 GBS patients and 1 CIDP patient on membranepotential and ionic currents in rat single myelinated nerve fibers was investigated using the voltage clamp technique and compared with that of the anti-GMl negative antisera obtained from 3 healthy controls and 2GBSpatients. Results In the presence of active complement, anti-GMl positive antisera from 5 patients including 4 GBSpatients and 1 CIDPpatient significantly suppressed Na+current more than anti-GMl negative antisera. Conclusion This study supports the notion that antiGMlantibody is one of the causative factors of conduction abnormality in GBSpatients.

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Acute conduction block in vitro following exposure to antiganglioside sera

Cited by 104 publications

References 23 publications

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice

The neuropathic potential of anti-GM1 autoantibodies is regulated by the local glycolipid environment in mice

A somatically mutated human antiganglioside IgM antibody that induces experimental neuropathy in mice is encoded by the variable region heavy chain gene, V1-18.

The Sera from GM1 Ganglioside Antibody Positive Patients with Guillain-Barre Syndrome or Chronic Inflammatory Demyelinating Polyneuropathy Blocks Na+ Currents in Rat Single Myelinated Nerve Fibers.

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