同济大学学报（医学版）2026，Vol.47Issue(2)：184-193,10.DOI:10.12289/j.issn.2097-4345.25206
散发性肌萎缩侧索硬化症的外周免疫特征
Peripheral immune characteristics of sporadic amyotrophic lateral sclerosis
摘要
Abstract
Objective To investigate the peripheral immune characteristics of sporadic amyotrophic lateral sclerosis(sALS).Methods Bulk RNA-seq data of peripheral blood mononuclear cells(PBMCs)from sALS patients and healthy controls were selected via the GEO database,followed by classification based on inflammation levels,differential gene expression analysis,and enrichment analysis.Results sALS patients were stratified into high(H),medium(M),and low(L)inflammatory subgroups,with M and L subgroups constituting the majority(84.4％).Differential gene analysis revealed that the H subgroup was predominantly characterized by innate immune activation,while M and L subgroups exhibited similarities showing HIF-1α and leukocyte migration signaling perturbation.Additionally,the L subgroup demonstrated unique EOMES overexpression,suggesting T-cell homeostasis imbalance.Further significantly down-regulation of HIF-1α in PBMCs in both sALS and familial ALS(fALS)patients was observed,suggesting it may represent a common transcriptional signature in ALS.This observation is further supported by findings in the SOD1G93A mouse model,where Hif-1 α expression level in PBMCs was similarly markedly reduced,highlighting its cross-species conservation in ALS pathogenesis.Conclusion This study investigates the peripheral immune characteristics of sALS patients,establishes a novel disease stratification framework,and reveales the pervasive dysregulation of HIF-1α and leukocyte migration signaling pathways,laying a robust theoretical foundation for future therapeutic development.关键词
散发性肌萎缩索硬化症/PBMCs转录组测序/炎症/HIF-1α/EOMESKey words
sporadic amyotrophic lateral sclerosis/bulk RNA-seq of peripheral blood mononuclear cells/inflammation/HIF-1α/EOMES分类
医药卫生引用本文复制引用
杨雪妍,陈伟,高文霞,张春雪,孙毅..散发性肌萎缩侧索硬化症的外周免疫特征[J].同济大学学报（医学版）,2026,47(2):184-193,10.基金项目
国家自然科学基金重点项目(82030035) （82030035）
