Elevated Tribbles homolog 2–specific antibody levels in narcolepsy patients

摘要: Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness and attacks of muscle atonia triggered strong emotions (cataplexy). caused hypocretin (orexin) deficiency, paralleled dramatic loss in hypothalamic hypocretin-producing neurons. It believed that narcolepsy an autoimmune disorder, although definitive proof this, such as the presence autoantibodies, still lacking. We engineered transgenic mouse model to identify peptides enriched within neurons could serve potential targets. Initial analysis indicated transcript encoding Tribbles homolog 2 (Trib2), previously identified autoantigen uveitis, was these mice. ELISA showed sera from patients with cataplexy had higher Trib2-specific antibody titers compared either normal controls or idiopathic hypersomnia, multiple sclerosis, other inflammatory neurological disorders. were highest early after onset, sharply decreased 2-3 years, then stabilized at levels substantially than for up 30 years. High correlated severity cataplexy. Serum patient specific immunoreactivity over 86% hypothalamus. Thus, we have reactive autoantibodies human narcolepsy, providing evidence disorder.