Serum factor in Miller-Fisher variant of Guillain-Barré syndrome and neurotransmitter release

doi:10.1016/S0140-6736(94)92694-8

The Lancet

Volume 343, Issue 8895, 19 February 1994, Pages 454-455

https://doi.org/10.1016/S0140-6736(94)92694-8 Get rights and content

Abstract

Serum IgG autoantibodies to GQ1b ganglioside are associated with the acute phase of the Miller-Fisher syndrome (MFS). We investigated the effects of three anti-GQ1b-positive MFS sera in the mouse phrenic-nerve/diaphragm preparation. Miniature endplate potential frequencies increased eight-fold within 25 min, declined rapidly, and ceased altogether after 3 h, when nerve stimulation no longer evoked a response. One MFS convalescent serum (anti-GQ1b negative) and sera from healthy controls and from patients with other neurological diseases were without effect. Thus muscle weakness in MFS may be caused by a serum factor, likely to be GQ1b antibody, that leads to failure of acetylcholine release from motor nerve terminals.

References (9)

Hj Willison et al.
Gangliosides and bacterial toxins in Guillain-Barré syndrome
J Neuroimmunol
(1993)
B. Lang et al.
Autoimmune aetiology for myasthenic (Eaton-Lambert) syndrome
Lancet
(1981)
M. Fisher
An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia)
N Engl J Med
(1956)
A. Chiba et al.
Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome
Ann Neurol
(1992)

There are more references available in the full text version of this article.

Cited by (145)

Guillain-Barré syndrome: Clinical variants and their pathogenesis
2011, Journal of Neuroimmunology
Citation Excerpt :
Some of the features of MF syndrome resemble myasthenia gravis and for this reason the neuromuscular junction appeared worth of study to see if GQ1b antibodies might influence neuromuscular junction function in a separate and novel way to anti-acetyl choline receptor antibodies. Two separate studies found abnormalities in vitro in neuromuscular junction preparations mediated by the serum of patients with MFS (Roberts, Willison et al., 1994; Plomp, Molenaar et al., 1999) and also by monoclonal antibodies against GQ1b(Goodyear, O'Hanlon et al., 1999). Such monoclonal antibodies could be seen to fix complement and cause NM junction disruption in the experimental model (Goodyear, O'Hanlon et al., 1999).
The co-occurrence of serologically proven myasthenia gravis and Miller Fisher/Guillain Barré overlap syndrome - A case report
2009, Journal of the Neurological Sciences
The co-occurrence of myasthenia gravis (MG) and Guillain Barré syndrome (GBS) is uncommon with a few reported cases in the literature. There is only one reported case of MG and Miller Fisher variant of GBS. We described an 84 year old Chinese woman with underlying seropositive myasthenia gravis (MG) who presented with ophthalmoplegia, areflexia and acute neuromuscular weakness. She was proved to have co-occurrence of MG and GBS/Miller Fisher overlap syndrome with positive anti-GQ1b antibody. The unusual finding in this patient raises an interesting question on their pathogenesis with the possibility that prior activation of the immune system may predispose the development of autoantibodies against other antigens within the same set of muscles.
The role of complement and complement regulators in mediating motor nerve terminal injury in murine models of Guillain-Barré syndrome
2008, Journal of Neuroimmunology
Recent research into the Guillain–Barré syndromes (GBS) has focused on anti-ganglioside antibodies that correlate with specific clinical phenotypes. Our increasing understanding of the role of antibodies in mediating GBS has naturally focused our attention on complement involvement in the pathological procession. We have studied the axonal and glial components of the murine motor nerve terminal as a model site of antibody and complement mediated injury. Such studies are providing us with clear information on the molecular components underlying our clinicopathological model for GBS and have lead us to the testing of emerging complement therapeutics that are potentially suitable for human use.
Anti-GQ1b antibody does not affect neuromuscular transmission in human limb muscle
2007, Journal of Neuroimmunology
Anti-ganglioside GQ1b antibody induces neuromuscular blocking on mouse phrenic nerve–diaphragm preparations. Several reports suggest that patients with this antibody show abnormal neuromuscular transmission in the facial or limb muscles, but limb muscle weakness is unusual in Miller Fisher syndrome that is often associated with anti-GQ1b antibody. To determine whether anti-GQ1b sera affect neuromuscular transmission in human limb muscles, axonal-stimulating single fiber electromyography was performed in the forearm muscle of seven patients with anti-GQ1b antibody. All showed normal jitter and no blocking. Anti-GQ1b antibody does not affect neuromuscular transmission in human limb muscles. The different findings in mouse and human may be explained by the extent of expression of GQ1b on the motor nerve terminals in the muscle examined.
Functional Effects of Autoantibodies
2006, The Autoimmune Diseases, Fourth Edition
The functional autoantibodies have provided new insights into potential pathophysiologic mechanisms in numerous autoimmune diseases. Early detection of these autoantibodies and their removal by immunotherapy offers an additional approach to treatment that may halt disease progression and prevent the chronic irreversible changes that are typical of autoimmune disease. There is likely to be a large family of functional autoantibodies. The earliest functional autoantibodies detected in the neurologic diseases myasthenia gravis, Lambert–Eaton myasthenic syndrome (LEMS), and neuromyotonia, have their parallel in naturally occurring genetic disorders affecting the skeletal muscle nicotinic receptor, P/Q-type voltage-gated calcium channels (VGCCs), and voltage-gated potassium channels (VGKCs). It seems more than reasonable to assume that autoimmune equivalents can also be detected for diseases affecting other ion channels or receptors. It is noted that a better understanding of these autoantibodies is likely to enhance greatly our ability to diagnose, monitor, and treat the associated autoimmune diseases.
Guillain-Barré syndrome
2005, Lancet
Citation Excerpt :
That there was no effect could be explained by the need for prolonged application of the antibody to its epitope to exert its effect. However, some researchers99–101 have shown that antibodies to GQ1b cause initial massive excitation and eventual conduction block at the GQ1b-rich motor-nerve terminals in the mouse phrenic nerve-diaphragm preparation. Most recently, both monoclonal mouse antibodies to GD1a and serum from a patient with AMAN containing antibodies to GD1a were shown to cause excitation and eventual conduction block of motor axons in the same preparation from mice over-expressing GD1a.102
Guillain-Barré syndrome consists of at least four subtypes of acute peripheral neuropathy. Major advances have been made in understanding the mechanisms of some of the subtypes. The histological appearance of the acute inflammatory demyelinating polyradiculoneuropathy (AIDP) subtype resembles experimental autoimmune neuritis, which is predominantly caused by T cells directed against peptides from the myelin proteins P0, P2, and PMP22. The role of T-cell-mediated immunity in AIDP remains unclear and there is evidence for the involvement of antibodies and complement. Strong evidence now exists that axonal subtypes of Guillain-Barré syndrome, acute motor axonal neuropathy (AMAN), and acute motor and sensory axonal neuropathy (AMSAN), are caused by antibodies to gangliosides on the axolemma that target macrophages to invade the axon at the node of Ranvier. About a quarter of patients with Guillain-Barré syndrome have had a recent Campylobacter jejuni infection, and axonal forms of the disease are especially common in these people. The lipo-oligosaccharide from the C jejuni bacterial wall contains ganglioside-like structures and its injection into rabbits induces a neuropathy that resembles acute motor axonal neuropathy. Antibodies to GM1, GM1b, GD1a, and GalNac-GD1a are in particular implicated in acute motor axonal neuropathy and, with the exception of GalNacGD1a, in acute motor and sensory axonal neuropathy. The Fisher's syndrome subtype is especially associated with antibodies to GQ1b, and similar cross-reactivity with ganglioside structures in the wall of C jejuni has been discovered. Anti-GQ1b antibodies have been shown to damage the motor nerve terminal in vitro by a complement-mediated mechanism. Results of international randomised trials have shown equivalent efficacy of both plasma exchange and intravenous immunoglobulin, but not corticosteroids, in hastening recovery from Guillain-Barré syndrome. Further research is needed to discover treatments to prevent 20% of patients from being left with persistent and significant disability.

View all citing articles on Scopus

View full text

Short reportsSerum factor in Miller-Fisher variant of Guillain-Barré syndrome and neurotransmitter release

Abstract

J Neuroimmunol

Lancet

An unusual variant of acute idiopathic polyneuritis (syndrome of ophthalmoplegia, ataxia and areflexia)

N Engl J Med

Serum IgG antibody to ganglioside GQ1b is a possible marker of Miller Fisher syndrome

Ann Neurol

Short reports
Serum factor in Miller-Fisher variant of Guillain-Barré syndrome and neurotransmitter release