Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, France.
Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, UPS, Toulouse, France; Department of Neurology, Toulouse University Hospitals, Toulouse, France.
J Neuroimmunol. 2024 Aug 15;393:578383. doi: 10.1016/j.jneuroim.2024.578383. Epub 2024 Jun 1.
NT1 is a rare, chronic and disabling neurological disease causing excessive daytime sleepiness and cataplexy. NT1 is characterized pathologically by an almost complete loss of neurons producing the hypocretin (HCRT)/orexin neuropeptides in the lateral hypothalamus. While the exact etiology of NT1 is still unknown, numerous studies have provided compelling evidence supporting its autoimmune origin. The prevailing hypothetical view on the pathogenesis of NT1 involves an immune-mediated loss of HCRT neurons that can be triggered by Pandemrix® vaccination and/or by infection in genetically susceptible patients, specifically carriers of the HLA-DQB1*06:02 MHC class II allele. The molecular mechanisms by which infection/vaccination can induce autoimmunity in the case of NT1 remain to be elucidated. In this review, evidence regarding the involvement of vaccination and infection and the potential mechanisms by which it could be linked to the pathogenesis of NT1 will be discussed in light of the existing findings in other autoimmune diseases.
NT1 是一种罕见的慢性和致残性神经系统疾病，可导致日间过度嗜睡和猝倒。NT1 的病理学特征是外侧下丘脑产生食欲素（HCRT）/orexin 神经肽的神经元几乎完全丧失。虽然 NT1 的确切病因仍不清楚，但许多研究提供了令人信服的证据，支持其自身免疫起源。关于 NT1 发病机制的流行假设观点涉及免疫介导的 HCRT 神经元丧失，这可能由 Pandemrix®疫苗接种和/或遗传易感患者（特别是 HLA-DQB1*06:02 MHC 类 II 等位基因携带者）的感染引发。感染/疫苗接种如何在 NT1 病例中引发自身免疫的分子机制仍有待阐明。在这篇综述中，将根据其他自身免疫性疾病的现有发现，讨论疫苗接种和感染的证据以及它与 NT1 发病机制相关的潜在机制。
