Kornum Birgitte Rahbek, Pizza Fabio, Knudsen Stine, Plazzi Giuseppe, Jennum Poul, Mignot Emmanuel
Center for Sleep Sciences and Medicine, Department of Psychiatry, Stanford University School of Medicine, Palo Alto, CA, USA; Molecular Sleep Laboratory, Department of Diagnostics, Rigshospitalet, Glostrup, Denmark; Danish Center for Sleep Medicine, Department of Neurophysiology, University of Copenhagen, Rigshospitalet, Glostrup, Denmark.
Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy; IRCCS Istituto delle Scienze Neurologiche di Bologna, AUSL di Bologna, Bologna, Italy.
Brain Behav Immun. 2015 Oct;49:54-8. doi: 10.1016/j.bbi.2015.03.004. Epub 2015 Mar 11.
Type 1 narcolepsy is caused by a loss of hypocretin (orexin) signaling in the brain. Genetic data suggests the disorder is caused by an autoimmune attack on hypocretin producing neurons in hypothalamus. This hypothesis has however not yet been confirmed by consistent findings of autoreactive antibodies or T-cells in patient samples. One explanation for these negative results may be that the autoimmune process is no longer active when patients present to the clinic. With increasing awareness in recent years, more and more patients have been diagnosed closer and closer to disease onset. In this study, we tested whether an active immune process in the brain could be detected in these patients, as reflected by increased cytokine levels in the cerebrospinal fluid (CSF). Using multiplex analysis, we measured the levels of 51 cytokines and chemokines in the CSF of 40 type 1 narcolepsy patients having varying disease duration. For comparison, we used samples from 9 healthy controls and 9 patients with other central hypersomnia. Cytokine levels did not differ significantly between controls and patients, even in 5 patients with disease onset less than a month prior to CSF sampling.
1型发作性睡病是由大脑中下丘脑分泌素(食欲素)信号缺失引起的。遗传数据表明,该疾病是由针对下丘脑分泌素产生神经元的自身免疫攻击所致。然而,这一假设尚未通过在患者样本中一致发现自身反应性抗体或T细胞得到证实。这些阴性结果的一种解释可能是,当患者就诊时,自身免疫过程已不再活跃。近年来,随着认识的提高,越来越多的患者在越来越接近疾病发作时被诊断出来。在本研究中,我们测试了这些患者大脑中是否能检测到活跃的免疫过程,这可通过脑脊液(CSF)中细胞因子水平升高来反映。我们采用多重分析方法,测量了40例病程各异的1型发作性睡病患者脑脊液中51种细胞因子和趋化因子的水平。为作比较,我们使用了9名健康对照者和9名患有其他中枢性过度嗜睡症患者的样本。即使在脑脊液采样前发病不到一个月的5例患者中,对照组和患者之间的细胞因子水平也没有显著差异。