Cao Yuan, Yao Wen, Chen Fang
Department of Ophthalmology, Northern Jiangsu People's Hospital, Yangzhou University, Yangzhou, China.
Front Genet. 2024 Aug 22;15:1423584. doi: 10.3389/fgene.2024.1423584. eCollection 2024.
Neuromyelitis Optica spectrum disorder (NMOSD) is an autoimmune disease characterized by anti-aquaporin-4 (AQP4) auto-antibodies. The discovery of antibodies AQP4 and myelin oligodendrocyte glycoprotein (MOG) has expanded our understanding of the pathogenesis of neuromyelitis optica. However, the molecular mechanisms underlying the disease, particularly AQP4-associated optic neuritis (AQP4-ON), remain to be fully elucidated.
In this study, we utilized Weighted Gene Co-expression Network Analysis (WGCNA) to investigate the transcriptomic profiles of peripheral blood samples from patients with AQP4-ON and MOG-positive optic neuritis (MOG-ON), compared to healthy controls.
WGCNA revealed a brown module (ME brown) strongly associated with AQP4-ON, which correlated positively with post-onset visual acuity decline. A total of 132 critical genes were identified, mainly involved in histone modification and microtubule dynamics. Notably, genes HDAC4, HDAC7, KDM6A, and KDM5C demonstrated high AUC values in ROC analysis, indicating their potential as biomarkers for AQP4-ON.
Our findings provide novel insights into the molecular signature of AQP4-ON and highlight the potential of systems biology approaches in identifying biomarkers for NMOSD. The identified histone modification genes warrant further investigation for their role in disease pathogenesis and as therapeutic targets.
视神经脊髓炎谱系障碍（NMOSD）是一种以抗水通道蛋白4（AQP4）自身抗体为特征的自身免疫性疾病。AQP4抗体和髓鞘少突胶质细胞糖蛋白（MOG）的发现扩展了我们对视神经脊髓炎发病机制的理解。然而，该疾病的分子机制，尤其是AQP4相关视神经炎（AQP4-ON），仍有待充分阐明。
在本研究中，我们利用加权基因共表达网络分析（WGCNA）来研究AQP4-ON患者和MOG阳性视神经炎（MOG-ON）患者外周血样本的转录组谱，并与健康对照进行比较。
WGCNA显示一个棕色模块（ME brown）与AQP4-ON密切相关，它与发病后视力下降呈正相关。共鉴定出132个关键基因，主要参与组蛋白修饰和微管动力学。值得注意的是，HDAC4、HDAC7、KDM6A和KDM5C基因在ROC分析中显示出高AUC值，表明它们作为AQP4-ON生物标志物的潜力。
我们的研究结果为AQP4-ON的分子特征提供了新的见解，并突出了系统生物学方法在识别NMOSD生物标志物方面的潜力。所鉴定的组蛋白修饰基因在疾病发病机制中的作用及其作为治疗靶点的潜力值得进一步研究。
