Antibodies in narcolepsy-cataplexy patient serum bind to rat hypocretin neurons.
Autoimmunity is considered the most likely cause of human narcolepsy-cataplexy, but no specific autoantibodies or antigen(s) have yet been identified. By means of indirect avidin-biotin immunohistochemical method, we searched for antibodies in serum from narcolepsy-cataplexy patients and controls that bind to rat hypocretin neurons. No staining was found in eight out of nine narcolepsy-cataplexy patients or controls. The serum from one narcolepsy-cataplexy patient, however, strongly produced staining of the membrane and superficial cytoplasm of neurons in the lateral hypothalamus. Dual staining revealed that the vast majority of the hypocretin-positive neurons were positive, but nonhypocretin neurons in the same area were binding antibodies from the patient's serum. These results show that antibodies bind to specific hypocretin- and nonhypocretin-containing neurons in the hypothalamus and indicate the presence of autoantibodies in narcolepsy patients.
Knudsen
Stine
S
Department of Clinical Neurophysiology, Danish Center for Sleep Medicine, University Hospital of Glostrup, Denmark.
Mikkelsen
Jens D
JD
Jennum
Poul
P
D000293:Adolescent; D000328:Adult; D000818:Animals; D000906:Antibodies / Q000097:blood* / Q000276:immunology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007026:Hypothalamic Area, Lateral / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009290:Narcolepsy / Q000097:blood* / Q000276:immunology*; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D051381:Rats
D000906:Antibodies; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins