Neurological Sciences and Cerebrovascular Research Laboratory, Department of Neurology, Neurology and Cerebrovascular Disease Group, Neuroscience Area of Hospital La Paz Institute for Health Research-IdiPAZ (La Paz University Hospital-Universidad Autónoma de Madrid), 28046 Madrid, Spain.
Proteomics Unit, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain.
Int J Mol Sci. 2024 Oct 6;25(19):10761. doi: 10.3390/ijms251910761.
Multiple sclerosis (MS) remains the leading cause of neurological disability among young adults worldwide, underscoring the urgent need to define the best therapeutic strategy. Recent advances in proteomics have deepened our understanding of treatment mechanisms and revealed promising biomarkers for predicting therapeutic outcomes. This study focuses on the identification of a protein profile of circulating extracellular vesicles (EVs) derived from neurons, oligodendrocytes, and B and T cells able to differentiate treatment responders and non-responders in 80 patients with MS. In the patients who responded to treatment, T cell-derived EVs were enriched in LV151, a protein involved in the promotion of anti-inflammatory cytokines, whereas Bcell-derived EVs showed elevated PSMD6 and PTPRC, related to immunoproteasome function. Oligodendrocyte- and neuron-derived EVs showed upregulated CO6A1 and COEA1, involved in extracellular matrix reorganisation, as well as LAMA5, NonO, SPNT, and NCAM, which are critical for brain repair. In contrast, non-responders showed higher levels of PSMD7 and PRS10 from B cell-derived EVs, associated with DNA damage, and increased levels of PERM and PERL from T cell-derived EVs, linked to nuclear factor kappa B activation and drug-resistant proteins such as HS90A and RASK. These findings highlight a distinct panel of proteins in EVs that could serve as an early indicator of treatment efficacy in MS.
多发性硬化症（MS）仍然是全球年轻成年人中导致神经功能障碍的主要原因，这突显了明确最佳治疗策略的迫切需要。蛋白质组学的最新进展加深了我们对治疗机制的理解，并揭示了有前途的生物标志物，可用于预测治疗效果。本研究专注于鉴定源自神经元、少突胶质细胞、B 细胞和 T 细胞的循环细胞外囊泡（EVs）的蛋白质谱，以区分 80 名 MS 患者中的治疗应答者和无应答者。在对治疗有反应的患者中，T 细胞衍生的 EVs 富含 LV151，这是一种参与促进抗炎细胞因子的蛋白质，而 B 细胞衍生的 EVs 显示出较高的 PSMD6 和 PTPRC，与免疫蛋白酶体功能有关。少突胶质细胞和神经元衍生的 EVs 显示出上调的 CO6A1 和 COEA1，参与细胞外基质的重新组织，以及 LAMA5、NonO、SPNT 和 NCAM，它们对大脑修复至关重要。相比之下，无应答者显示出更高水平的 B 细胞衍生 EVs 中的 PSMD7 和 PRS10，与 DNA 损伤有关，以及 T 细胞衍生 EVs 中的 PERM 和 PERL 水平升高，与核因子 kappa B 激活和耐药蛋白（如 HS90A 和 RASK）有关。这些发现突出了 EVs 中一组独特的蛋白质，它们可以作为 MS 治疗效果的早期指标。
