Project description:Genome wide DNA methylation profiling of CD4 T cells from treated and untreated patients with multiple sclerosis. The Illumina InfiniumEPIC methylation Beadchip was used to obtain DNA methylation profiles across approximately 850,000 CpGs of CD4 T cells from patients with multiple sclerosis.
Project description:The aim of this study was to identify differentially expressed genes in peripheral blood mononuclear cells from MS patients that were responders or non-responders to the neuroantigen myelin basic protein. Using microarray we measured mRNA-expression levels in freshly isolated peripheral blood mononuclear cells from 17 untreated patients with multiple sclerosis. Based on studies, measuring the responses of blood derived T-cells to myelin basic protein ex vivo, these 17 untreated MS-patients can be divided into two groups: 4 of the untreated multiple sclerosis patients had T-cells that responded to myelin basic protein ex vivo whereas 13 untreated MS patients had T-cells that did not respond to myelin basic protein ex vivo.
Project description:Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female MS specimens before pregnancy with respect to female MS specimens at ninth month pregnancy. Subjects were followed in the outpatients clinic and blood was collected before pregnancy and at the following time points during pregnancy: first trimester (gestational age at sampling 12 weeks), second trimester (24 weeks), and third trimester (36 weeks). Before-pregnancy samples were obtained in a treatment-free period and after anticonceptional drug withdrawal. Peripheral blood mononuclear cells (PBMCs) obtained from 17 women (8 MS patients before pregnancy and 9 MS patients at 9th month pregnancy) were analyzed by oligonucleotide microarray technology.
Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed transcriptomics in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the RNA-seq.
Project description:Patient with multiple sclerosis improves during pregnancy while temporarily worsening post-partum. The reasons behind the disease modulation during pregnancy remain unknown. In this study, we have investigated the effect of pregnancy on circulating CD4+ and CD8+ T cells from patients with multiple sclerosis and healthy controls to gain a deeper understanding why patients with multiple sclerosis improves during pregnancy. We assessed epigenome-wide DNA methylation in CD4+ and CD8+ T cells obtained during (1st, 2nd and 3rd trimester) and after pregnancy (6 weeks post-partum), using the Infinium MethylationEPIC 850K array.
Project description:Multiple sclerosis (MS) is a severe chronic inflammatory disease of the central nervous system (CNS) that leads to disability in young adults. T lymphocytes are a key component of lesion pathology throughout the disease course. Here we used the animal model experimental autoimmune encephalomyelitis (EAE) to conduct an unbiased characterization of CD4+ T cells in acute and chronic EAE.
Project description:Circular RNAs (circRNAs) have emerged as a new type of endogenous non-coding RNA characterized by their covalently closed circular structure and a backspliced junction (BSJ) resulting from a back-splicing process. In the last years, several studies have shown that circRNAs are important modulators in the immune system, activation of inflammation, antibacterial and antiviral responses as well as autoimmune diseases, such as multiple sclerosis. In the last years, it has been proposed that a subset of circRNA form imperfect double-stranded structures that allow them to interact with PKR (double stranded RNA-activated protein kinase), an intracellular protein responsible for recognizing long double stranded RNAs, usually viral RNAs, in the cytoplasm and trigger an anti-viral response of the cell. Taking into account the implication of the innate immune response in multiple sclerosis pathophysiology and the discovery of circRNA deregulation in multiple sclerosis patients, we wanted to investigate the circRNA-PKR crosstalk and its implication in the pathology of multiple sclerosis. Using an in vitro model of the anti-viral response and RNA-seq to characterize circRNA expression, we observed that poly (I:C) (a double-stranded RNA) stimulation produces a global downregulation of circRNA, PKR phosphorylation and immune-related gene activation and that these effects are reversed when treatment is stopped. Additionally, we found that the overexpression of double stranded RNA-containing circRNAs is able to reduce the PKR phosphorylation and the activation of immune-related pathways induced by poly(I:C). Finally, we measured the PKR phosphorylation in PBMCs isolated from multiple sclerosis patients in relapse and remission phases, but we did not obtain conclusive results since there is a very big variability between samples. In conclusion, this work reinforces the evidence on the mechanism describing the interaction between PKR and circRNA containing double-stranded structures and their role in the immune response. Besides, our experiments highlight the importance of the structure in circRNA function. Lastly, it also sheds some light into the possible implication of the circRNA-PKR axis in multiple sclerosis although further research is needed to make a better characterization of this mechanism in order to understand its potential role in the regulation of the immune response of the disease.
Project description:Background: pregnancy is associated with reduced activity of multiple sclerosis (MS). However, the biological mechanisms underlying this pregnancy-related decrease in disease activity are poorly understood. This data series contains the subset of data used to generate a MS signature comparing female MS specimens before pregnancy with respect to female MS specimens at ninth month pregnancy.
