You Huajing, Wu Tengteng, Du Gang, Huang Yue, Zeng Yixuan, Lin Lishan, Chen Dingbang, Wu Chao, Li Xunhua, Burgunder Jean-Marc, Pei Zhong
Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases, National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, China.
Front Neurol. 2021 Nov 19;12:779890. doi: 10.3389/fneur.2021.779890. eCollection 2021.
Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder. Neurofilament light protein (NfL) is correlated with clinical severity of HD but relative data are the lack in the Chinese population. Reactive astrocytes are related to HD pathology, which predicts their potential to be a biomarker in HD progression. Our aim was to discuss the role of blood glial fibrillary acidic protein (GFAP) to evaluate clinical severity in patients with HD. Fifty-seven HD mutation carriers (15 premanifest HD, preHD, and 42 manifest HD) and 26 healthy controls were recruited. Demographic data and clinical severity assessed with the internationally Unified Huntington's Disease Rating Scale (UHDRS) were retrospectively analyzed. Plasma NfL and GFAP were quantified with an ultra-sensitive single-molecule (Simoa, Norcross, GA, USA) technology. We explored their consistency and their correlation with clinical severity. Compared with healthy controls, plasma NfL ( < 0.0001) and GFAP ( < 0.001) were increased in Chinese HD mutation carriers, and they were linearly correlated with each other ( = 0.612, < 0.001). They were also significantly correlated with disease burden, Total Motor Score (TMS) and Total Functional Capacity (TFC). The scores of Stroop word reading, symbol digit modalities tests, and short version of the Problem Behaviors Assessments (PBAs) for HD were correlated with plasma NfL but not GFAP. Compared with healthy controls, plasma NfL has been increased since stage 1 but plasma GFAP began to increase statistically in stage 2. Plasma GFAP was correlated with plasma NfL, disease burden, TMS, and TFC in HD mutation carriers. Plasma GFAP may have potential to be a sensitive biomarker for evaluating HD progression.
亨廷顿舞蹈症（HD）是一种常染色体显性神经退行性疾病。神经丝轻链蛋白（NfL）与HD的临床严重程度相关，但在中国人群中相关数据较少。反应性星形胶质细胞与HD病理学相关，这预示着它们有可能成为HD进展的生物标志物。我们的目的是探讨血液中胶质纤维酸性蛋白（GFAP）在评估HD患者临床严重程度中的作用。招募了57名HD突变携带者（15名症状前HD患者，即preHD，以及42名症状性HD患者）和26名健康对照者。回顾性分析了人口统计学数据以及使用国际统一亨廷顿舞蹈症评定量表（UHDRS）评估的临床严重程度。采用超灵敏单分子（Simoa，美国佐治亚州诺克罗斯）技术对血浆NfL和GFAP进行定量分析。我们探究了它们之间的一致性以及与临床严重程度的相关性。与健康对照者相比，中国HD突变携带者的血浆NfL（<0.0001）和GFAP（<0.001）升高，且二者呈线性相关（r = 0.612，P < 0.001）。它们还与疾病负担、总运动评分（TMS）和总功能能力（TFC）显著相关。HD患者的斯特鲁普单词阅读、符号数字模式测试以及问题行为评估（PBA）简版的得分与血浆NfL相关，但与GFAP无关。与健康对照者相比，血浆NfL从第1阶段就开始升高，但血浆GFAP在第2阶段才开始出现统计学意义上的升高。在HD突变携带者中，血浆GFAP与血浆NfL、疾病负担、TMS和TFC相关。血浆GFAP有可能成为评估HD进展的敏感生物标志物。
