奥克雷珠单抗会改变复发缓解型多发性硬化症患者的循环代谢组。

IF 4.4 2区 医学 Q1 CLINICAL NEUROLOGY Annals of Clinical and Translational Neurology Pub Date : 2024-08-26 DOI:10.1002/acn3.52167
Fatemeh Siavoshi, Dimitrios C. Ladakis, Ashley Muller, Bardia Nourbakhsh, Pavan Bhargava
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引用次数: 0

摘要

背景:多发性硬化症(MS)患者的循环代谢物水平会发生改变,并与 MS 的严重程度有关。然而,奥克立珠单抗等高效疗法后代谢谱如何变化仍不清楚:多发性硬化症(MS)患者的循环代谢物水平会发生改变,并与MS的严重程度有关。然而,奥克立珠单抗等高效疗法后代谢谱如何变化仍不清楚。目的:评估复发性多发性硬化症(RRMS)患者接受奥克立珠单抗治疗后循环代谢组的变化:招募了31名有资格开始接受奥克立珠单抗治疗的RRMS患者,并对他们进行随访,每次随访都收集人口统计学、临床、生活质量和全球代谢组学数据。采用加权相关网络分析方法确定了高度相关的代谢物模块。使用线性混合效应模型评估了研究期间每个模块的代谢物特征值和单个代谢物的变化:患者的平均年龄为 40.8 (SD = 10.30)岁,中位病程为 4.0 (IQR = 8.5)年,接受监测的中位时间为 3.36 (IQR = 1.43)年。在已确定的十二组代谢物中,有两组发生了显著变化。第一个模块主要包含雄激素类固醇和孕烯醇酮类固醇(p 值 解释性说明:在这项纵向观察研究中,我们采用了一种全局非靶向代谢组学方法,结果显示接受奥克立珠单抗治疗的 RRMS 患者的循环代谢组发生了显著变化。特别是,我们观察到参与溶血磷脂通路的代谢物明显减少,这与患者病情的改善有关。
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Ocrelizumab alters the circulating metabolome in people with relapsing–remitting multiple sclerosis

Background

Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear.

Objective

Circulating metabolite levels are altered in multiple sclerosis (MS) and are associated with MS severity. However, how metabolic profiles shift following highly efficacious therapies, like ocrelizumab remains unclear. To assess changes in the circulating metabolome produced by ocrelizumab treatment in people with relapsing–remitting MS (RRMS).

Methods

Thirty-one individuals with RRMS eligible for beginning treatment with ocrelizumab were recruited and followed with demographic, clinical, quality-of-life, and global metabolomics data collected at each visit. Modules of highly correlated metabolites were identified using the weighted correlation network analysis approach. Changes in each module's eigenmetabolite values and individual metabolites during the study were evaluated using linear mixed-effects models.

Results

Patients with a mean age of 40.8 (SD = 10.30) years, and median disease duration of 4.0 (IQR = 8.5) years, were monitored for a median of 3.36 (IQR = 1.43) years. Two out of twelve identified sets of metabolites were altered significantly. The first module mainly contained androgenic and pregnenolone steroids (p-value <0.001, coefficient: −0.10). The second module primarily consisted of several lysophospholipids, arachidonic acid, some endocannabinoids, and monohydroxy fatty acid metabolites (p-value = 0.016, coefficient: −0.12), which its reduction was significantly associated with improvement based on overall disability response score (OR 3.09e-01, 95% CI: 6.83e-02, 9.09e-01, p-value = 3.15E-02).

Interpretation

In this longitudinal observational study, using a global untargeted metabolomics approach, we showed significant alteration in circulating metabolome in RRMS patients undergoing ocrelizumab treatment. In particular, we observed a significant reduction in metabolites involved in the lysophospholipid pathway, which was associated with patients' improvement.

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来源期刊
Annals of Clinical and Translational Neurology
Annals of Clinical and Translational Neurology Medicine-Neurology (clinical)
CiteScore
9.10
自引率
1.90%
发文量
218
审稿时长
8 weeks
期刊介绍: Annals of Clinical and Translational Neurology is a peer-reviewed journal for rapid dissemination of high-quality research related to all areas of neurology. The journal publishes original research and scholarly reviews focused on the mechanisms and treatments of diseases of the nervous system; high-impact topics in neurologic education; and other topics of interest to the clinical neuroscience community.
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