Immunolocalization of GQ1b and related gangliosides in human extraocular neuromuscular junctions and muscle spindles.
OBJECTIVE
To examine the distribution of anti-GQ1b, -GT1a, and -GD1b antibody binding in human extraocular muscles (EOMs), axial and limb muscles, and muscle spindles and thereby test the hypothesis that their distinctive ganglioside composition provides the molecular basis for selective involvement of EOMs and muscle spindles in Miller Fisher syndrome.


METHODS
Muscle samples from adult human EOMs, vastus lateralis, biceps brachii, lumbrical, psoas, and deep muscles of the neck were processed for immunohistochemistry, with monoclonal antibodies against ganglioside GQ1b, GT1a, and GD1b. Neuromuscular junctions (NMJs) were detected by alpha-bungarotoxin binding and by acetyl cholinesterase reaction.


RESULTS
Most motor endplates of human EOMs richly bound anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies. Anti-GQ1b, -GT1a, and -GD1b ganglioside antibody bindings to NMJs in human limb and axial muscle were scarce, but the nerve terminals inside muscle spindles and in direct contact with intrafusal fibers were labeled with anti- GQ1b, -GT1a, and -GD1b ganglioside antibodies.


CONCLUSIONS
The abundant and synaptic-specific binding of anti-GQ1b, -GT1a, and -GD1b ganglioside antibodies and the rich capillary supply in the human EOMs may partly explain the selective paralysis of these muscles in Miller Fisher syndrome.
Liu
Jing-Xia
JX
Department of Integrative Medical Biology, Section for Anatomy, Umeå University, Umeå, Sweden.
Willison
Hugh J
HJ
Pedrosa-Domellöf
Fatima
F
D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D019846:Miller Fisher Syndrome / Q000378:metabolism*; D009470:Muscle Spindles / Q000378:metabolism*; D009334:Neck Muscles / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009801:Oculomotor Muscles / Q000378:metabolism*; D016658:Psoas Muscles / Q000378:metabolism; D055815:Young Adult
D000911:Antibodies, Monoclonal; D005732:Gangliosides; C033851:ganglioside, GD1b; C016481:trisialoganglioside GT1; C039129:GQ1b ganglioside