Dataset Information

Treatment choice matters in multiple sclerosis: The role of extracellular vesicles in predicting treatment response.

ABSTRACT: Multiple sclerosis (MS) is an immune-mediated central nervous system disease whose course is unpredictable. Finding biomarkers that help to better comprehend thedisease’s pathogenesis iscrucial for supporting clinical decision-making. Blood extracellular vesicles (EVs) are membrane-bound particles secreted by all cell types that contain information on the disease’s pathological processes.This study aimed to identify the immune and nervous system-associated EV profile in blood that could have a specific role as biomarker in MS. We also assessed the possible correlation between this EV profile with disease activity and cognitive and motor dysfunction in patients with MS. For this propose, we analyzed the levels, diameter and protein content of circulating nervous and immune system-derived EVs in the blood of patients with MS compared to the EVs found in another immune-mediated disease (rheumatoid arthritis) and in another white matter lesion (subcortical stroke) to determine the contribution of these EVs to autoimmunity and brain damage.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, T Cell, Oligodendrocyte, Neuron Maturation, Blood

DISEASE(S): Multiple Sclerosis,Stroke,Rheumatoid Arthritis

SUBMITTER: Susana Bravo

LAB HEAD: Susana Bravo

PROVIDER: PXD038003 | Pride | 2025-10-20

REPOSITORIES: Pride

ACCESS DATA

Dataset's files

Source:

			Action	DRS
	Pool_B_Lymphocyte-derived_EVs_from_healthy_controls_1.wiff	Wiff
	Pool_B_Lymphocyte-derived_EVs_from_healthy_controls_1.wiff.scan	Wiff
	Pool_B_Lymphocyte-derived_EVs_from_healthy_controls_2.wiff	Wiff
	Pool_B_Lymphocyte-derived_EVs_from_healthy_controls_2.wiff.scan	Wiff
	Pool_B_Lymphocyte-derived_EVs_from_healthy_controls_3.wiff	Wiff

Items per page:

1 - 5 of 146

Publications

Extracellular Vesicles as Novel Biomarkers for Tumor Association in Intermediate-Risk Paraneoplastic Neurologic Syndromes.

Torres Iglesias Gabriel G Chavarría-Miranda Alba A López-Molina MariPaz M Del Fresno Carlos C Mata-Martínez Pablo P Nozal Pilar P Chico-Garcia Juan Luis JL Fernández-Fournier Mireya M Lacruz Ballester Laura L Sanchez Darío D Montero-Calle Ana A Barderas Rodrigo R Bravo Susana S Puertas Inmaculada I York Elisa E Díez-Tejedor Exuperio E Gutiérrez-Fernández María M Otero-Ortega Laura L

Neurology(R) neuroimmunology & neuroinflammation 20251010 6

<h4>Background and objectives</h4>Paraneoplastic neurologic syndromes (PNS) are cancer-related neurologic disorders caused by an autoimmune response targeting both the tumor and the nervous system. Identifying new biomarkers for early cancer detection could improve treatment outcomes. Tumor-derived cells release extracellular vesicles (EVs) carrying tumor-specific molecular signatures, which can help distinguish patients with cancer even in early stages. The aim of this study was to assess the p ...[more]

PMID: 41071973

Similar Datasets

Project description:In the last two decades, several disease-modifying treatments (DMTs) have been developed for MS. These therapies are based on the modulation of the immune system and the aim to reduce the disease activity. However, as the natural course of the disease is unpredictable, the benefit of each treatment in each individual patient is still unknown and clinical decisions are very complicated. Some patients initiate treatment but continue with relapses, new lesions in the central nervous system, or show worsening disability. When this occurs, the response of the treatment is considered suboptimal and has to be switched to a more effective treatment, albeit generally with a higher risk of serious adverse effects. Currently, these decisions are made on a case-by-case basis when the lesions in the CNS and the increase in disability have occurred. This is likely due to multiple factors, including the absence of highly predictive, widely used treatment response biomarkers with reasonable sensitivity and specificity that step over the disease heterogeneity and that can be applied in real-life clinical practice. As a result, a high percentage of MS patients do not present adequate control of their disease activity while receiving DMT. In this context, a biomarker that anticipates treatment response or predicts treatment failure would help to make the change before irreversible injury occurs. We aim to analyse whether proteins and miRNAs derived from patients' circulating EVs could provide relevant information about the patient's response to treatment. To build on this, we assessed EV levels, size, microRNA, and protein content from neurons, oligodendrocytes, B and T lymphocytes, pre- and 3 months post-treatment initiation, and correlated with therapeutic response over 12 months in MS patients. Treatment response treatment was evaluated using ‘no evidence of disease activity’ (NEDA5) composite that includes the following clinical parameters: clinical relapses, new lesions on MRI, motor and cognitive disability progression and brain atrophy.

Project description:Background: Acute coronary syndromes (ACS) are associated with aberrant gene expression and epigenetic mechanisms. In particular, de novo DNA methylation is typically linked to gene silencing, but its role in heart disease remains not fully understood. Extracellular vesicles (EVs) are active components in cellular communication for their ability to carry a plethora of signalling biomolecules, thus representing a promising new diagnostic/therapeutic approach in cardiovascular diseases (CVDs). Indeed, there is the need of novel biomarkers for ACS prediction and timely detection. Purpose: We hypothesized that specific epigenetic signals can be carried by EVs. In this regard, we isolated and characterized circulating EVs from ACS patients and evaluated their potential role to influence DNA methylation in target cells. Methods: Circulating EVs were recovered, by ultracentrifugation, from plasma samples of 19 ACS patients and 50 healthy subjects (HS). Nanoparticle tracking analysis (NTA) and western blot (WB) were used to confirm the EVs integrity and purity. Peripheral blood mononuclear cells (PBMCs) of volunteer donors were treated with both ACS and HS derived EVs and genomic DNA was extracted to perform epigenome wide analysis through Reduced Representation Bisulfite Sequencing. ShinyGO, PANTHER, and STRING tools were interrogated to perform GO and PPI network analyses. Flow Cytometry, qRT-PCR, and WB analysis were also performed to evaluate and validate both intra-vesicular and intra-cellular signals. Results: Plasma ACS-derived EVs showed a significant up-regulation of DNA methyltransferases (DNMTs) gene expression levels as compared to HS (P<0.001). Specifically, de novo methylation transcripts, as DNMT3A and DNMT3B were significantly increased in plasma ACS-EVs. DNA methylation analysis of PBMCs from volunteer donors treated with HS- and ACS-derived EVs showed that RNF166 and CCND3 genes resulted the most hyper- and hypo-methylated, respectively, after by ACS-EV treatment. In addition, PPI network analysis specifically evidenced the subnetwork with SRC, as a hub gene, connecting it to NOTCH1, FOXO3, CDC42, IKBKG, RXRA, DGKG, known as important genes already involved in the onset of CVDs. Surprising, other novel genes, BAIAP2, SYP, CHL1, and SHB, which were hypomethylated, were found significantly overexpressed in PBMCs (P<0.005), underlying the fundamental modulating properties of EV cargo in atherosclerosis. Conclusions: These findings support the significant role of ACS plasma-derived EVs, inducing de novo DNA methylation signals, and modulating specific signaling pathways in target cells.