Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), University of Toulouse, CNRS, INSERM, Toulouse, France.
Department of Immunology, Toulouse University Hospitals, Toulouse, France.
Nat Rev Immunol. 2024 Jan;24(1):33-48. doi: 10.1038/s41577-023-00902-9. Epub 2023 Jul 3.
Narcolepsy type 1 (NT1) is a chronic sleep disorder resulting from the loss of a small population of hypothalamic neurons that produce wake-promoting hypocretin (HCRT; also known as orexin) peptides. An immune-mediated pathology for NT1 has long been suspected given its exceptionally tight association with the MHC class II allele HLA-DQB1*06:02, as well as recent genetic evidence showing associations with polymorphisms of T cell receptor genes and other immune-relevant loci and the increased incidence of NT1 that has been observed after vaccination with the influenza vaccine Pandemrix. The search for both self-antigens and foreign antigens recognized by the pathogenic T cell response in NT1 is ongoing. Increased T cell reactivity against HCRT has been consistently reported in patients with NT1, but data demonstrating a primary role for T cells in neuronal destruction are currently lacking. Animal models are providing clues regarding the roles of autoreactive CD4 and CD8 T cells in the disease. Elucidation of the pathogenesis of NT1 will allow for the development of targeted immunotherapies at disease onset and could serve as a model for other immune-mediated neurological diseases.
发作性睡病 1 型（NT1）是一种慢性睡眠障碍，其病因是下丘脑神经元数量减少，而这些神经元会产生促进觉醒的食欲素（HCRT；也称为食欲肽）肽。鉴于其与 MHC Ⅱ类等位基因 HLA-DQB1*06:02 异常紧密相关，以及最近的遗传证据表明与 T 细胞受体基因和其他免疫相关基因座的多态性以及流感疫苗 Pandemrix 接种后观察到的 NT1 发病率增加有关，因此长期以来一直怀疑 NT1 存在免疫介导的病理机制。目前仍在寻找 NT1 中致病性 T 细胞反应识别的自身抗原和外源抗原。一直有报道称，NT1 患者的 T 细胞对 HCRT 的反应性增加，但目前缺乏 T 细胞在神经元破坏中起主要作用的证据。动物模型为自身反应性 CD4 和 CD8 T 细胞在疾病中的作用提供了线索。阐明 NT1 的发病机制将允许在疾病发作时开发针对特定靶点的免疫疗法，并可作为其他免疫介导的神经疾病的模型。
