Deng Qi, Tang Cuiling, Chen Zhao, Yuan Xinrong, Ding Ziyan, Wang Chunrong, Wan Linlin, Hu Jian, Deng Feiyan, Long Zhe, He Lang, Peng Linliu, Lei Lijing, Yuan Hongyu, Wan Na, Gong Yiqing, Tan Yan, Ding Siyu, Tang Beisha, Qiu Rong, Jiang Hong
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Key Laboratory of Hunan Province in Neurodegenerative Disorders, Central South University, Changsha, Hunan, China.
Mov Disord. 2025 Jul;40(7):1379-1387. doi: 10.1002/mds.30189. Epub 2025 Apr 10.
The immune system likely plays a role in the pathogenesis of spinocerebellar ataxia type 3 (SCA3). Peripheral blood leukocytes are indicative of the immune status in neurodegenerative diseases. However, alterations in the characteristics of peripheral blood leukocytes at different stages of SCA3 and their potential roles in disease progression remain unclear.
The goal was to identify leukocyte profiles alterations at different stages of SCA3 and analyze their correlation with disease severity.
This cross-sectional study included 150 total ATXN3 expansion carriers (20 pre-ataxic and 130 ataxic) and 113 healthy controls. Differences in leukocyte profiles were analyzed, and correlations with clinical characteristics were assessed using Spearman and partial correlation. Logistic regression and receiver operating characteristic curve identified independent factors associated with disease severity. Mediation analysis evaluated the effect of lymphocyte counts on the relationship between disease duration and SARA scores.
Alterations in neutrophil, lymphocyte, eosinophil, and basophil counts were observed across ATXN3 expansion carriers, including those in pre-ataxic and ataxic stages, compared with healthy controls. Lymphocyte counts negatively correlated with SARA and International Cooperative Ataxia Rating Scale scores, particularly in speech function. Leukocyte, monocyte, and basophil counts were also negatively associated with ataxia scales scores or sub-item scores. Lymphocyte counts distinguished disease severities, and partially mediated the effect of disease duration on ataxia scale scores in ataxic SCA3.
Leukocyte profiles alterations at different stages of SCA3 may be closely linked to disease progression and severity. Lymphocyte counts may serve as valuable indicators of disease severity. © 2025 International Parkinson and Movement Disorder Society.
免疫系统可能在3型脊髓小脑共济失调（SCA3）的发病机制中起作用。外周血白细胞可反映神经退行性疾病中的免疫状态。然而，SCA3不同阶段外周血白细胞特征的变化及其在疾病进展中的潜在作用仍不清楚。
本研究旨在确定SCA3不同阶段白细胞谱的变化，并分析其与疾病严重程度的相关性。
本横断面研究纳入了150名ATXN3基因扩增携带者（20名共济失调前期患者和130名共济失调患者）和113名健康对照。分析白细胞谱的差异，并使用Spearman和偏相关分析评估其与临床特征的相关性。逻辑回归和受试者工作特征曲线确定与疾病严重程度相关的独立因素。中介分析评估淋巴细胞计数对疾病持续时间与SARA评分之间关系的影响。
与健康对照相比，在ATXN3基因扩增携带者中观察到中性粒细胞、淋巴细胞、嗜酸性粒细胞和嗜碱性粒细胞计数的变化，包括共济失调前期和共济失调期。淋巴细胞计数与SARA和国际合作共济失调评定量表评分呈负相关，尤其是在言语功能方面。白细胞、单核细胞和嗜碱性粒细胞计数也与共济失调量表评分或子项目评分呈负相关。淋巴细胞计数可区分疾病严重程度，并部分介导疾病持续时间对共济失调SCA3患者共济失调量表评分的影响。
SCA3不同阶段白细胞谱的变化可能与疾病进展和严重程度密切相关。淋巴细胞计数可能是疾病严重程度的重要指标。© 2025国际帕金森病和运动障碍协会
