Integrated omics profiling reveals systemic dysregulation and potential biomarkers in the blood of patients with neuromyelitis optica spectrum disorders.

IF 5.3 2区 材料科学 Q2 MATERIALS SCIENCE, MULTIDISCIPLINARY
Zuoquan Xie, Qinming Zhou, Jin Hu, Lu He, Huangyu Meng, Xiaoni Liu, Guangqiang Sun, Zhiyu Luo, Yuan Feng, Liang Li, Xingkun Chu, Chen Du, Dabing Yang, Xinying Yang, Jing Zhang, Changrong Ge, Xiang Zhang, Sheng Chen, Meiyu Geng
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引用次数: 0

Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: 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.

综合全息图谱分析揭示了神经脊髓炎视网膜频谱疾病患者血液中的系统失调和潜在生物标记物。
背景:神经脊髓炎视网膜频谱疾病(NMOSD)是一种影响中枢神经系统的自身免疫性疾病。外周异常对该病发病机制的影响尚不十分清楚:为了研究这个问题,我们采用了一种多组学方法来分析 52 名 NMOSD 患者和 46 名健康对照者(HC)的血液样本。这包括质谱、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,我们还进行了综合分析,以确定 NMOSD 与 HC 的区别特征。此外,我们还揭示了 NMOSD 不同临床亚组间外周特征的差异。我们利用一个由40名NMOSD患者组成的独立队列来评估血清中成纤维细胞活化蛋白α(FAP)的水平:结果:我们的分析揭示了 NMOSD 患者独特的外周免疫和代谢特征。该特征的特点是单核细胞增多,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,我们还发现炎性细胞因子水平升高,而组织修复细胞因子水平降低。代谢变化也很明显,胆汁酸、乳酸盐、甘油三酯水平升高,而硫酸脱氢表雄酮、高精氨酸、十八碳二烯酸(FA[18:2])和鞘脂水平降低。我们发现了区分 NMOSD 和 HC 的独特生物标志物,并发现了与疾病严重程度相关的血液因子。其中,成纤维细胞活化蛋白α(FAP)是疾病进展的显著标记物:我们的综合血液特征分析为了解 NMOSD 病理生理学提供了新的视角,揭示了显著的外周免疫和代谢改变。这项工作为未来 NMOSD 的生物标志物鉴定和机理研究奠定了基础,并强调了 FAP 作为疾病进展标志物的潜力。
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来源期刊
CiteScore
8.30
自引率
3.40%
发文量
1601
期刊介绍: ACS Applied Nano Materials is an interdisciplinary journal publishing original research covering all aspects of engineering, chemistry, physics and biology relevant to applications of nanomaterials. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important applications of nanomaterials.
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