Stanford Center for Sleep Sciences and Medicine, Stanford University School of Medicine, 1050 A, Arastradero Road, Palo Alto, CA 94034, USA.
Curr Opin Neurobiol. 2013 Oct;23(5):767-73. doi: 10.1016/j.conb.2013.04.013. Epub 2013 May 29.
Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. Narcolepsy is caused by the loss of hypocretin (orexin)-producing neurons in the lateral hypothalamus. Evidence, such as a strong association with HLA DQB1*06:02, strongly suggests an autoimmune basis targeting hypocretin neurons. Genome-wide association studies have strengthened the association between narcolepsy and immune system gene polymorphisms, including the identification of polymorphisms in the T cell receptor alpha locus, TNFSF4 (also called OX40L), Cathepsin H (CTSH) the purinergic receptor P2RY11, and the DNA methyltransferase DNMT1. Recently, attention has been raised regarding a spike in cases of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1) in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Europe. How the immune system may be involved in disease initiation and/or progression remains a challenge to researchers. Potential immunological pathways that could lead to the specific elimination of hypocretin producing neurons include molecular mimicry or bystander activation, and are likely a combination of genetic and environmental factors, such as upper airway infections.
发作性睡病是一种以日间过度嗜睡、猝倒、催眠幻觉、睡眠瘫痪和夜间睡眠模式紊乱为特征的神经退行性疾病。发作性睡病是由外侧下丘脑产生食欲素（orexin）的神经元丧失引起的。有强有力的证据，如与 HLA DQB1*06:02 强烈相关，强烈提示其具有针对食欲素神经元的自身免疫基础。全基因组关联研究加强了发作性睡病与免疫系统基因多态性之间的关联，包括在 T 细胞受体 alpha 基因座、TNFSF4（也称为 OX40L）、组织蛋白酶 H (CTSH)、嘌呤能受体 P2RY11 和 DNA 甲基转移酶 DNMT1 中发现的多态性。最近，人们开始关注中国 2009 年 H1N1 大流行（pH1N1）后，2010 年儿童发作性睡病病例的激增，以及在欧洲使用的含佐剂 H1N1 疫苗 Pandemrix 的接种情况。免疫系统如何参与疾病的发生和/或进展仍然是研究人员面临的一个挑战。可能导致特定的食欲素产生神经元被消除的潜在免疫途径包括分子模拟或旁观者激活，可能是遗传和环境因素的组合，例如上呼吸道感染。
