Combined pre- and postsynaptic action of IgG antibodies in Miller Fisher syndrome.
BACKGROUND
Miller Fisher syndrome (MFS), a variant of the Guillain-Barré syndrome, is associated with the presence of neuromuscular blocking antibodies, some of which may be directed at the ganglioside GQ1b.


METHODS
The authors investigated the in vitro effects of serum and purified immunoglobulin (Ig) G in a total of 11 patients with typical MFS during active disease, and in three of those patients after recovery. From one patient's serum, we prepared an IgG fraction enriched in anti-GQ1b antibodies by affinity chromatography. For combined pre- and postsynaptic analysis, endplate currents were recorded by a perfused macro-patch clamp electrode. Postsynaptic nicotinic acetylcholine receptor channels were investigated by an outside-out patch clamp technique in cultured mouse myotubes.


RESULTS
AllMFS-sera depressed evoked quantal release and reduced the amplitude of postsynaptic currents. Five of the 11 sera were additionally examined by outside-out patch clamp analysis and caused a concentration-dependent and reversible decrease in acetylcholine-induced currents. The time course of activation and desensitization of nicotinic acetylcholine receptor channels was not altered by MFS-IgG. Nine patients (82 %) were positive for anti-GQ1b antibodies in ELISA and dot-blot. The enriched anti-GQ1b antibody fraction had a similar effect as whole serum. After recovery from MFS, blocking activity was lost and sera originally positive for anti-GQ1b antibodies became negative.


CONCLUSIONS
Circulating IgG antibodies induce both pre- and postsynaptic blockade and may play a pathogenic role in acute MFS.
Buchwald
B
B
Neurologische Klinik der Bayerischen Julius-Maximilians-Universität Würzburg, Germany. brigitte.buchwald@mail.uni-wuerzburg.de
Bufler
J
J
Carpo
M
M
Heidenreich
F
F
Pitz
R
R
Dudel
J
J
Nobile-Orazio
E
E
Toyka
K V
KV
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D002478:Cells, Cultured; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000276:immunology; D005260:Female; D005732:Gangliosides / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000302:isolation & purification / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D019846:Miller Fisher Syndrome / Q000276:immunology*; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000502:physiology; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011978:Receptors, Nicotinic / Q000276:immunology / Q000378:metabolism; D013569:Synapses / Q000276:immunology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000276:immunology; D014665:Vasodilator Agents / Q000494:pharmacology
D001323:Autoantibodies; D005732:Gangliosides; D007074:Immunoglobulin G; D018377:Neurotransmitter Agents; D011978:Receptors, Nicotinic; D014665:Vasodilator Agents; C039129:GQ1b ganglioside; D000109:Acetylcholine