Narcolepsy and the HLA region.
Narcolepsy was first shown to be tightly associated with HLA-DR2 and DQ1 in 1983, suggesting a possible autoimmune mechanism. Early investigations failed to demonstrate this hypothesis, postulating that HLA-DR2 was only a linkage marker for another, unknown narcolepsy-causing gene. The autoimmune hypothesis is now being re-evaluated under the light of recent results. Like many other autoimmune disorders, narcolepsy usually starts during adolescence, is human leukocyte antigen (HLA)-associated, multigenic and environmentally influenced. Furthermore, HLA-association studies indicated a primary HLA-DQ effect with complex HLA class II allele interactions and a partial contribution of HLA to overall genetic susceptibility. Finally, recent result suggests that human narcolepsy is associated with the destruction of a small number of hypothalamic neurons containing the peptide hypocretins (orexins). This data is consistent with an immune destruction of hypocretin-containing cells as the most common etiology for human narcolepsy.
Lin
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Department of Psychiatry and Behavioral Sciences, Stanford Center for Narcolepsy, Stanford University Medical Center, 1201 Welch Road, P-114, Palo Alto, CA 94305-5485, USA.
Hungs
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Mignot
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D000595:Amino Acid Sequence; D000818:Animals; D015551:Autoimmunity; D002352:Carrier Proteins / Q000502:physiology; D004285:Dogs; D006683:HLA-DQ Antigens / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D015802:HLA-DR2 Antigen / Q000737:chemistry / Q000235:genetics* / Q000502:physiology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D009290:Narcolepsy / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D009479:Neuropeptides / Q000502:physiology; D000068797:Orexins; D013329:Structure-Activity Relationship
D002352:Carrier Proteins; D006683:HLA-DQ Antigens; C051568:HLA-DQ1 antigen; D015802:HLA-DR2 Antigen; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins