title: [Narcolepsy as an autoimmune disease].
abstract: Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness and irresistible sleep attacks that occur during the activities of daily living. Falling asleep in the middle of essential activities such as driving or crossing the street may lead to life-threatening situations. Narcolepsy is estimated to affect 0.002% of the Israeli population. By using animal models, human autopsies and brain biopsies, it has recently been shown that the destruction of the orexin-secreting neurons underlies the pathogenicity of this disease. Orexin is a neurotransmitter involved in the sleep arousal cycle and also in the development of hunger sensations. Based on circumstantial evidence, it is estimated that the autoimmune system is responsible for the destruction of the orexin-secreting neurons. There are several findings in the literature that might connect the autoimmunity with the narcolepsy existence. For instance: narcolepsy is associated with high frequency of specific HLA system alleles, especially DQB1*0602. Furthermore, polymorphism in the alpha chain of the T cell receptors was found among narcolepsy patients. A more direct connection is the discovery of the Trib--an autoantigen. This protein is presented by orexin-secreting neurons and was recently found in narcoleptic patients exclusively, and not in the healthy control group. Nevertheless, there is still no agreement within the scientific community since a direct link between the autoimmune mechanism and narcolepsy has not yet been proved. Several trials using immune modulator therapy did not show any significant improvement.
authors.affiliation: Department of Neurology, Sheba Medical Center. gili.givaty@sheba.health.gov.il
authors.forename: Gili
authors.initials: G
authors.lastname: Givaty
authors.forename: Esther
authors.initials: E
authors.lastname: Ganelin-Cohen
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000453:epidemiology / Q000276:immunology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D006680:HLA Antigens / Q000276:immunology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000276:immunology / Q000378:metabolism*; D007557:Israel / Q000453:epidemiology; D009290:Narcolepsy / Q000453:epidemiology / Q000276:immunology*; D009474:Neurons / Q000473:pathology; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins
chemical_list: D006680:HLA Antigens; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C489044:TRIB2 protein, human