Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal

G.M. O'Hanlon, J.J. Plomp, M. Chakrabarti, I. Morrison, E.R. Wagner, C.S. Goodyear, X. Yin, B.D. Trapp, J. Conner, P.C. Molenaar, S. Stewart, E.G. Rowan, H.J. Willison

Research output: Contribution to journalArticle

137 Citations (Scopus)

Abstract

Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent {alpha}-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III ß-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.
LanguageEnglish
Pages893-906
Number of pages13
JournalBrain
Volume124
Issue number5
DOIs
Publication statusPublished - 2001

Fingerprint

Anti-Idiotypic Antibodies
Miller Fisher Syndrome
Motor Endplate
Ophthalmoplegia
Neuromuscular Blockade
Antibodies
Gangliosides
Schwann Cells
Presynaptic Terminals
Ataxia
Tubulin
Fluorescence Microscopy
Acetylcholine
Electron Microscopy
Wounds and Injuries
GQ1b ganglioside
neurofilament protein H
alpha-latrotoxin

Keywords

  • brain
  • biomedical science
  • neuropathy
  • ataxia
  • areflexia
  • ophthalmoplegia
  • autoantibody
  • complement
  • ganglioside
  • miller-fisher syndrome
  • neuromuscular junction

Cite this

O'Hanlon, G. M., Plomp, J. J., Chakrabarti, M., Morrison, I., Wagner, E. R., Goodyear, C. S., ... Willison, H. J. (2001). Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal. Brain, 124(5), 893-906. https://doi.org/10.10.1093/brain/124.5.893
O'Hanlon, G.M. ; Plomp, J.J. ; Chakrabarti, M. ; Morrison, I. ; Wagner, E.R. ; Goodyear, C.S. ; Yin, X. ; Trapp, B.D. ; Conner, J. ; Molenaar, P.C. ; Stewart, S. ; Rowan, E.G. ; Willison, H.J. / Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal. In: Brain. 2001 ; Vol. 124, No. 5. pp. 893-906.
@article{5f1cadaf3ea544a798b5b6f34a7aa8ff,
title = "Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal",
abstract = "Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent {alpha}-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III {\ss}-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.",
keywords = "brain, biomedical science, neuropathy, ataxia, areflexia, ophthalmoplegia, autoantibody, complement, ganglioside, miller-fisher syndrome, neuromuscular junction",
author = "G.M. O'Hanlon and J.J. Plomp and M. Chakrabarti and I. Morrison and E.R. Wagner and C.S. Goodyear and X. Yin and B.D. Trapp and J. Conner and P.C. Molenaar and S. Stewart and E.G. Rowan and H.J. Willison",
year = "2001",
doi = "10.10.1093/brain/124.5.893",
language = "English",
volume = "124",
pages = "893--906",
journal = "Brain",
issn = "0006-8950",
number = "5",

}

O'Hanlon, GM, Plomp, JJ, Chakrabarti, M, Morrison, I, Wagner, ER, Goodyear, CS, Yin, X, Trapp, BD, Conner, J, Molenaar, PC, Stewart, S, Rowan, EG & Willison, HJ 2001, 'Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal' Brain, vol. 124, no. 5, pp. 893-906. https://doi.org/10.10.1093/brain/124.5.893

Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal. / O'Hanlon, G.M.; Plomp, J.J.; Chakrabarti, M.; Morrison, I.; Wagner, E.R.; Goodyear, C.S.; Yin, X.; Trapp, B.D.; Conner, J.; Molenaar, P.C.; Stewart, S.; Rowan, E.G.; Willison, H.J.

In: Brain, Vol. 124, No. 5, 2001, p. 893-906.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal

AU - O'Hanlon, G.M.

AU - Plomp, J.J.

AU - Chakrabarti, M.

AU - Morrison, I.

AU - Wagner, E.R.

AU - Goodyear, C.S.

AU - Yin, X.

AU - Trapp, B.D.

AU - Conner, J.

AU - Molenaar, P.C.

AU - Stewart, S.

AU - Rowan, E.G.

AU - Willison, H.J.

PY - 2001

Y1 - 2001

N2 - Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent {alpha}-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III ß-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.

AB - Miller-Fisher syndrome is an autoimmune neuropathy characterized by ataxia, areflexia and ophthalmoplegia, and in the majority of cases the presence of high titres of anti-GQ1b ganglioside antibodies. In an ex vivo model, human and mouse anti-GQ1b antibodies have been shown previously to induce a complement-dependent {alpha}-latrotoxin-like effect on the murine motor endplate, i.e. they bring about massive quantal release of acetylcholine and eventually block neuromuscular transmission. Using immunofluorescence microscopy with image analysis, we show here that the late stages of this electrophysiological effect temporally coincide with the loss of heavy neurofilament (200 kDa) and type III ß-tubulin immunostaining and structural breakdown of the nerve terminal, as demonstrated by electron microscopy. Ultrastructurally, axon terminals were disorganized, depleted of vesicles, and subdivided by the infiltrating processes of capping Schwann cells. These findings provide clear pathological evidence to support a role for anti-ganglioside antibodies in mediating nerve terminal injury and further advance the view that this site may be of importance as a target in some human neuropathies.

KW - brain

KW - biomedical science

KW - neuropathy

KW - ataxia

KW - areflexia

KW - ophthalmoplegia

KW - autoantibody

KW - complement

KW - ganglioside

KW - miller-fisher syndrome

KW - neuromuscular junction

UR - http://brain.oxfordjournals.org/cgi/content/abstract/124/5/893

UR - http://dx.doi.org/10.10.1093/brain/124.5.893

U2 - 10.10.1093/brain/124.5.893

DO - 10.10.1093/brain/124.5.893

M3 - Article

VL - 124

SP - 893

EP - 906

JO - Brain

T2 - Brain

JF - Brain

SN - 0006-8950

IS - 5

ER -

O'Hanlon GM, Plomp JJ, Chakrabarti M, Morrison I, Wagner ER, Goodyear CS et al. Anti-GQ1b ganglioside antibodies mediate complement-dependent destruction of the motor nerve terminal. Brain. 2001;124(5):893-906. https://doi.org/10.10.1093/brain/124.5.893