Department of Ophthalmology, Affiliated Wuxi Clinical College of Nantong University, Wuxi, Jiangsu, China.
Department of Ophthalmology, Jiangnan University Medical Center (JUMC), Wuxi, Jiangsu, China.
Front Immunol. 2023 Mar 9;14:1095966. doi: 10.3389/fimmu.2023.1095966. eCollection 2023.
To compare the different immunological mechanisms between aquaporin 4 antibody-associated optic neuritis (AQP4-ON) and myelin oligodendrocyte glycoprotein antibody-associated optic neuritis (MOG-ON) based on RNA sequencing (RNA-seq) of whole blood.
Whole blood was collected from seven healthy volunteers, 6 patients with AQP4-ON and 8 patients with MOG-ON, and used for RNA-seq analysis. An examination of immune cell infiltration was performed using the CIBERSORTx algorithm to identify infiltrated immune cells.
RNA-seq analysis showed that the inflammatory signaling was mainly activated by , , and in AQP4-ON patients, while which was mainly activated by , , , and in MOG-ON patients. Biological function identification of differentially expressed genes (DEGs) based on Gene Ontology (GO) term and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis, as well as Disease Ontology (DO) analysis, showed that the inflammation in AQP4-ON was likely mediated by damage-associated molecular pattern (DAMP), while which in MOG-ON was likely mediated by pathogen-associated molecular pattern (PAMP). Analysis of immune cell infiltration showed that the proportion of immune cell infiltration was related to patients' vision. The infiltration ratios of monocytes (rs=0.69, =0.006) and M0 macrophages (rs=0.66, =0.01) were positively correlated with the BCVA (LogMAR), and the infiltration ratio of neutrophils was negatively correlated with the BCVA (LogMAR) (rs=0.65, =0.01).
This study reveals different immunological mechanisms between AQP4-ON and MOG-ON based on transcriptomics analysis of patients' whole blood, which may expand the current knowledge regarding optic neuritis.
基于全血 RNA 测序（RNA-seq）比较水通道蛋白 4 抗体相关性视神经炎（AQP4-ON）和髓鞘少突胶质细胞糖蛋白抗体相关性视神经炎（MOG-ON）的不同免疫机制。
采集 7 名健康志愿者、6 名 AQP4-ON 患者和 8 名 MOG-ON 患者的全血进行 RNA-seq 分析。使用 CIBERSORTx 算法对免疫细胞浸润进行检测，以鉴定浸润的免疫细胞。
RNA-seq 分析表明，AQP4-ON 患者的炎症信号主要由 、 、 和 激活，而 MOG-ON 患者的炎症信号主要由 、 、 、 和 激活。基于基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路富集分析以及疾病本体论（DO）分析对差异表达基因（DEGs）进行生物学功能鉴定，结果显示 AQP4-ON 中的炎症可能由损伤相关分子模式（DAMP）介导，而 MOG-ON 中的炎症可能由病原体相关分子模式（PAMP）介导。免疫细胞浸润分析表明，免疫细胞浸润的比例与患者的视力有关。单核细胞（rs=0.69，=0.006）和 M0 巨噬细胞（rs=0.66，=0.01）的浸润比例与 BCVA（LogMAR）呈正相关，而中性粒细胞的浸润比例与 BCVA（LogMAR）呈负相关（rs=0.65，=0.01）。
本研究基于患者全血的转录组学分析揭示了 AQP4-ON 和 MOG-ON 之间不同的免疫机制，这可能扩展了对视神经炎的现有认识。
