Similar Datasets
Project description:Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. While CD4+Foxp3+ regulatory T cells (Tregs) play a central role in preventing autoimmunity, the molecular mechanism underlying their dysfunction is unknown. Here, we performed comprehensive transcriptional and epigenetic profiling of Tregs in multiple sclerosis (MS) to identify central transcriptional programs regulating human autoimmunity.
2024-09-30 | GSE209596 | GEO
Project description:Autoimmune diseases, among the most common disorders of young adults, are mediated by genetic and environmental factors. While CD4+Foxp3+ regulatory T cells (Tregs) play a central role in preventing autoimmunity, the molecular mechanism underlying their dysfunction is unknown. Here, we performed comprehensive transcriptional and epigenetic profiling of Tregs in multiple sclerosis (MS) to identify central transcriptional programs regulating human autoimmunity.
2024-09-30 | GSE274000 | GEO
Project description:Transcriptomic profiling of blood mTreg and mTeff from healthy control (HC) and multiple sclerosis (MS)
| PRJNA1144433 | ENA
Project description:Transcriptomic profiling of blood mTreg and mTeff from healthy control (HC) and multiple sclerosis (MS) [RNA-Seq]
| PRJNA861303 | ENA
Project description:Transcriptomic and epigenetic profiling of blood mTreg and mTeff from healthy control (HC) and multiple sclerosis (MS) [ATAC-Seq]
| PRJNA1144437 | ENA
Project description:Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). It is characterized by the infiltration of autoreactive immune cells into the CNS, which target the myelin sheath, leading to the loss of neuronal function. Although it is accepted that MS is a multifactorial disorder with both genetic and environmental factors influencing its development and course, the molecular pathogenesis of MS has not yet been fully elucidated. Here, we studied the longitudinal gene expression profiles of whole-blood RNA from a cohort of 195 MS patients and 66 healthy controls. We analyzed these transcriptomes at both the individual transcript and the biological pathway level. We found 62 transcripts to be significantly up-regulated in MS patients; the expression of 11 of these genes was counter-regulated by interferon treatment, suggesting partial restoration of a 'healthy' gene expression profile. Global pathway analyses linked the proteasome and Wnt signaling to MS disease processes. Since genotypes from a subset of individuals were available, we were able to identify expression quantitative trait loci (eQTL), a number of which involved two genes of the MS gene signature. However, all these eQTL were also present in healthy controls. This study highlights the challenge posed by analyzing transcripts from whole blood and how these can be mitigated by using large, well-characterized cohorts of patients with longitudinal follow-up and multi-modality measurements.
| S-EPMC3781642 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-08-02 | E-GEOD-43592 | biostudies-arrayexpress
Project description:Background: Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance. Methods: In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate. Results: In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r=0.6590, p=0.0104; linear regression analysis r=0.6577, p=0.0106). The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype. Conclusions: The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease.
2010-03-04 | GSE20334 | GEO
Project description:Background: Multiple sclerosis (MS) is a complex disorder thought to result from an interaction between environmental and genetic predisposing factors which have not yet been characterised, although it is known to be associated with the HLA region on 6p21.32. Recently, a picture of chronic cerebrospinal venous insufficiency (CCSVI), consequent to stenosing venous malformation of the main extra-cranial outflow routes (VM), has been described in patients affected with MS, introducing an additional phenotype with possible pathogenic significance. Methods: In order to explore the presence of copy number variations (CNVs) within the HLA locus, a custom CGH array was designed to cover 7 Mb of the HLA locus region (6,899,999bp; chr6:29,900,001-36,800,000). Genomic DNA of the 15 patients with CCSVI/VM and MS was hybridised in duplicate. Results: In total, 322 CNVs, of which 225 were extragenic and 97 intragenic, were identified in 15 patients. 234 known polymorphic CNVs were detected, the majority of these being situated in non-coding or extragenic regions. The overall number of CNVs (both extra- and intragenic) showed a robust and significant correlation with the number of stenosing VMs (Spearman: r=0.6590, p=0.0104; linear regression analysis r=0.6577, p=0.0106). The region we analysed contains 211 known genes. By using pathway analysis focused on angiogenesis and venous development, MS, and immunity, we tentatively highlight several genes as possible susceptibility factor candidates involved in this peculiar phenotype. Conclusions: The CNVs contained in the HLA locus region in patients with the novel phenotype of CCSVI/VM and MS were mapped in detail, demonstrating a significant correlation between the number of known CNVs found in the HLA region and the number of CCSVI-VMs identified in patients. Pathway analysis revealed common routes of interaction of several of the genes involved in angiogenesis and immunity contained within this region. Despite the small sample size in this pilot study, it does suggest that the number of multiple polymorphic CNVs in the HLA locus deserves further study, owing to their possible involvement in susceptibility to this novel MS/VM plus phenotype, and perhaps even other types of the disease. 8 female and 7 male MS patients
2010-03-03 | E-GEOD-20334 | biostudies-arrayexpress
Project description:We investigated the innate immune system in the SOD1 ALS model. We found that splenic Ly6CHi monocytes were activated and their progressive recruitment to the spinal cord, but not brain, correlated with neuronal loss. We found a decrease in resident microglia in the spinal cord with disease progression. Two months prior to disease onset, splenic Ly6CHi monocytes had an M1 signature which included increased CCR2. At one month prior to disease onset, microglia expressed increased CCL2 and other chemotaxis-associated molecules. Microglia derived from the spinal cord of SOD1 mice recruited Ly6C+ monocytes to the CNS. Treatment with anti-Ly6C mAb modulated the Ly6CHi monocyte cytokine profile, reduced monocyte recruitment to the spinal cord, diminished neuronal loss and extended survival. In humans with ALS, CD14+/CD16- monocytes (analogue of Ly6CHi monocytes) exhibited an ALS specific microRNA inflammatory signature similar to that observed in the SOD1 mouse providing a direct link between the animal model and the human disease. Thus, the SOD1-like profile of monocytes in ALS subjects may serve as a biomarker for disease stage or progression. Our results suggest that recruitment of inflammatory monocytes plays an important role in disease progression and that modulation of these cells is a potential therapeutic approach. This study used the NanoString nCounter hybridization system and nCounter miRNA expression assays to identify and quantitate miRNAs in blood CD14+CD16- monocytes from ALS, MS and HC subjects
2012-07-26 | GSE39643 | GEO