State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
Department of Neurology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200025, China.
J Transl Med. 2024 Nov 1;22(1):989. doi: 10.1186/s12967-024-05801-8.
Neuromyelitis optica spectrum disorders (NMOSD) are autoimmune conditions that affect the central nervous system. The contribution of peripheral abnormalities to the disease's pathogenesis is not well understood.
To investigate this, we employed a multi-omics approach analyzing blood samples from 52 NMOSD patients and 46 healthy controls (HC). This included mass cytometry, cytokine arrays, and targeted metabolomics. We then analyzed the peripheral changes of NMOSD, and features related to NMOSD's disease severity. Furthermore, an integrative analysis was conducted to identify the distinguishing characteristics of NMOSD from HC. Additionally, we unveiled the variations in peripheral features among different clinical subgroups within NMOSD. An independent cohort of 40 individuals with NMOSD was utilized to assess the serum levels of fibroblast activation protein alpha (FAP).
Our analysis revealed a distinct peripheral immune and metabolic signature in NMOSD patients. This signature is characterized by an increase in monocytes and a decrease in regulatory T cells, dendritic cells, natural killer cells, and various T cell subsets. Additionally, we found elevated levels of inflammatory cytokines and reduced levels of tissue-repair cytokines. Metabolic changes were also evident, with higher levels of bile acids, lactates, triglycerides, and lower levels of dehydroepiandrosterone sulfate, homoarginine, octadecadienoic acid (FA[18:2]), and sphingolipids. We identified distinctive biomarkers differentiating NMOSD from HC and found blood factors correlating with disease severity. Among these, fibroblast activation protein alpha (FAP) was a notable marker of disease progression.
Our comprehensive blood profile analysis offers new insights into NMOSD pathophysiology, revealing significant peripheral immune and metabolic alterations. This work lays the groundwork for future biomarker identification and mechanistic studies in NMOSD, highlighting the potential of FAP as a marker of disease progression.
视神经脊髓炎谱系疾病（NMOSD）是一种影响中枢神经系统的自身免疫性疾病。外周异常对疾病发病机制的影响尚不清楚。
为了研究这一点，我们采用多组学方法分析了 52 名 NMOSD 患者和 46 名健康对照者（HC）的血液样本。这包括质谱流式细胞术、细胞因子阵列和靶向代谢组学。然后，我们分析了 NMOSD 的外周变化，以及与 NMOSD 疾病严重程度相关的特征。此外，进行了综合分析以确定 NMOSD 与 HC 的区别特征。此外，我们还揭示了 NMOSD 不同临床亚组之间外周特征的变化。利用一个独立的 40 名 NMOSD 患者队列评估成纤维细胞激活蛋白α（FAP）的血清水平。
我们的分析揭示了 NMOSD 患者外周免疫和代谢特征的独特特征。该特征的特点是单核细胞增加，调节性 T 细胞、树突状细胞、自然杀伤细胞和各种 T 细胞亚群减少。此外，我们发现炎症细胞因子水平升高，组织修复细胞因子水平降低。代谢变化也很明显，胆汁酸、乳酸、甘油三酯水平升高，脱氢表雄酮硫酸酯、同型精氨酸、十八碳二烯酸（FA[18:2]）和鞘脂水平降低。我们确定了区分 NMOSD 与 HC 的独特生物标志物，并发现与疾病严重程度相关的血液因素。其中，成纤维细胞激活蛋白α（FAP）是疾病进展的一个显著标志物。
我们全面的血液谱分析为 NMOSD 病理生理学提供了新的见解，揭示了外周免疫和代谢的显著变化。这项工作为 NMOSD 中的未来生物标志物识别和机制研究奠定了基础，突出了 FAP 作为疾病进展标志物的潜力。
