摘要：

目的: 分析抗富亮氨酸胶质瘤失活蛋白1抗体相关脑炎（以下简称抗LGI1抗体相关脑炎）伴睡眠障碍患者血清和脑脊液生物学标志物的表达变化，并初步探讨其发病机制。方法: 纳入2015年4月至2022年9月河南省人民医院诊断与治疗的50例抗LGI1抗体相关脑炎患者，采集血清和脑脊液标本，测定神经损伤标志物[神经丝蛋白轻链（NfL）、胶质纤维酸性蛋白（GFAP）、离子钙结合蛋白1（Iba1）]、神经内分泌标志物（促食欲素A、皮质醇）和神经免疫标志物[白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、CXC趋化因子配体13（CXCL13）]，匹兹堡睡眠质量指数（PSQI）诊断睡眠障碍。结果: 共50例患者根据PSQI评分分为睡眠障碍组（> 7分，28例）和无睡眠障碍组（≤ 7分，22例）。与无睡眠障碍组相比，睡眠障碍组患者表现出更高的血清和脑脊液NfL（t = 6.690，P = 0.000；t = 2.356，P = 0.023）、GFAP（t = 3.713，P = 0.000；t = 2.768，P = 0.008）和Iba1（t = 5.042，P = 0.000；t = 3.472，P = 0.001），促食欲素A（t = 3.250，P = 0.002；t = 5.376，P = 0.000）和皮质醇（t = 2.487，P = 0.016；t = 5.779，P = 0.000），以及TNF-α（t = 3.832，P = 0.000；t = 5.122，P = 0.000）和CXCL13（t = 2.483，P = 0.017；t = 4.116，P = 0.000）水平，仅脑脊液IL-1β水平升高（t = 2.526，P = 0.015）。结论: 抗LGI1抗体相关脑炎伴睡眠障碍患者神经损伤标志物、神经内分泌标志物及神经免疫标志物表达水平均升高，提示疾病的发生并非单一机制，可能与神经-内分泌-免疫网络广泛受累有关。

关键词: 脑炎, 神经系统自身免疫疾病, 睡眠障碍, 生物标记

Abstract:

Objective: To analyze the changes in biomarkers associated with sleep disorders in anti-leucine-rich glioma-inactivated 1 (LGI1) antibody- associated encephalitis, and to preliminarily explore the mechanism of sleep disorders. Methods: Fifty patients with anti - LGI1 antibody - associated encephalitis who admitted He'nan Provincial People's Hospital from April 2015 to September 2022 were selected. Serum and cerebrospinal fluid (CSF) samples were collected for biomarkers detection, and Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the presence of sleep disorders. Results: The 50 patients were divided into the sleep disorders (> 7) group (n = 28) and the no sleep disorders (≤ 7) group (n = 22) based on PSQI score. Compared with the no sleep disorders group, the sleep disorders group in serum and CSF showed higher levels of neurofilament light chain (NfL; t = 6.690, P = 0.000; t = 2.356, P = 0.023), glial fibrillary acidic protein (GFAP; t = 3.713, P = 0.000; t = 2.768, P = 0.008), ionized calcium-binding adapter molecule 1 (Iba1; t = 5.042, P = 0.000; t = 3.472, P = 0.001), orexin A (t = 3.250, P = 0.002; t = 5.376, P = 0.000), cortisol (t = 2.487, P = 0.016; t = 5.779, P = 0.000), tumor necrosis factor-α (TNF-α; t = 3.832, P = 0.000; t = 5.122, P = 0.000) and chemokine (C-X-C motif) ligand 13 (CXCL13; t = 2.483, P = 0.017; t = 4.116, P = 0.000), while only interleukin-1β (IL-1β) increased in CSF (t = 2.526, P = 0.015). Conclusions: Sleep disorders associated with anti - LGI1 antibody - associated encephalitis is elevated in levels of neuroinjury markers, neuroendocrine markers and neuroimmune markers, suggesting that sleep disorders associated with anti-LGI1 antibody- associated encephalitis is not a single mechanism and may be related to the extensive involvement of the neuro-endocrine-immune network.

Key words: Encephalitis, Autoimmune diseases of the nervous system, Sleep disorders, Biomarkers