Immunohistochemical screening for autoantibodies against lateral hypothalamic neurons in human narcolepsy.
Most human patients with narcolepsy have no detectable hypocretin-1 in their cerebrospinal fluid. The cause of this hypocretin deficiency is unknown, but the prevailing hypothesis states that an autoimmune-mediated mechanism is responsible. We screened for the presence of autoantibodies against neurons in the lateral hypothalamus in 76 patients and 63 controls, using immunohistochemistry. Autoantibodies were present in two patients, but also in two controls. However, one of the patients had a clearly different staining pattern and nerve endings of immunolabeled cells were found to project onto hypocretin-producing neurons, suggesting a possible pathophysiological role. Humoral immune mechanisms appear not to play a role in the pathogenesis of narcolepsy, at least not in the clinically overt stage of the disease.
Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands. S.Overeem@neuro.umcn.nl
Sebastiaan
S
Overeem
Jan J
JJ
Verschuuren
Rolf
R
Fronczek
Liesbeth
L
Schreurs
Heleen
H
den Hertog
Ingrid M
IM
Hegeman-Kleinn
Sjoerd G
SG
van Duinen
Unga A
UA
Unmehopa
Dick F
DF
Swaab
Gert Jan
GJ
Lammers
D000328:Adult; D001323:Autoantibodies / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007026:Hypothalamic Area, Lateral / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism; D000068797:Orexins
D001323:Autoantibodies; C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins