scholarly journals Profiling of Plasma Extracellular Vesicle Transcriptome Reveals That circRNAs Are Prevalent and Differ between Multiple Sclerosis Patients and Healthy Controls

Biomedicines ◽  
2021 ◽  
Vol 9 (12) ◽  
pp. 1850
Author(s):  
Leire Iparraguirre ◽  
Ainhoa Alberro ◽  
Thomas B. Hansen ◽  
Tamara Castillo-Triviño ◽  
Maider Muñoz-Culla ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Differential Expression Analysis ◽  
Cell Types ◽  
Extracellular Vesicle ◽  
Circular Rnas ◽  
P Value ◽  
Healthy Controls ◽  
Rna Regulation ◽  
Type Distribution ◽  
Multiple Sclerosis Patients

(1) Background: Extracellular vesicles (EVs) are released by most cell types and are implicated in several biological and pathological processes, including multiple sclerosis (MS). Differences in the number and cargo of plasma-derived EVs have been described in MS. In this work, we have characterised the EV RNA cargo of MS patients, with particular attention to circular RNAs (circRNAs), which have attracted increasing attention for their roles in physiology and disease and their biomarker potential. (2) Methods: Plasma-derived EVs were isolated by differential centrifugation (20 patients, 8 controls), and RNA-Sequencing was used to identify differentially expressed linear and circRNAs. (3) Results: We found differences in the RNA type distribution, circRNAs being enriched in EVs vs. leucocytes. We found a number of (corrected p-value < 0.05) circRNA significantly DE between the groups. Nevertheless, highly structured circRNAs are preferentially retained in leukocytes. Differential expression analysis reports significant differences in circRNA and linear RNA expression between MS patients and controls, as well as between different MS types. (4) Conclusions: Plasma derived EV RNA cargo is not a representation of leukocytes’ cytoplasm but a message worth studying. Moreover, our results reveal the interest of circRNAs as part of this message, highlighting the importance of further understanding RNA regulation in MS.

scholarly journals Profiling of plasma extracellular vesicle transcriptome reveals that circRNAs are prevalent and differ between multiple sclerosis patients and healthy controls

2021 ◽  
Author(s):  
Leire Iparraguirre ◽  
Ainhoa Alberro ◽  
Thomas Birkballe Hansen ◽  
Tamara Castillo-Triviño ◽  
Maider Muñoz-Culla ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Differential Expression ◽  
Extracellular Vesicles ◽  
Expression Analysis ◽  
Secondary Structure Prediction ◽  
Differential Expression Analysis ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Type Distribution ◽  
Multiple Sclerosis Patients

Abstract Background Extracellular vesicles (EVs) are released by almost all cell types and are implicated in a number of biological and pathological processes including autoimmune diseases such as multiple sclerosis (MS). Differences in the number and cargo of plasma derived EVs have been described in MS. In this work, we attempt to characterise the EV RNA cargo of MS patients with particular attention to a recently discovered non coding RNA type, circular RNAs (circRNAs), which have been shown to play important roles in physiology and disease and hold a great biomarker potential. Methods Plasma was collected from 20 MS patients and 8 healthy controls (HC) and total RNA was isolated from plasma-derived extracellular vesicles isolated by differential centrifugation. Samples were pooled in disease status, sex and age paired groups and RNA-Sequenced with Illumina HiSeq X Ten after rRNA depletion. CircRNAs were detected by both find_circ and CIRI2 and their quantification was based on BSJ-spanning reads. Linear transcripts were quantified by HTSEq. Differential expression analysis was performed using DESeq2. RNA type distribution was analyzed based on biomart classification. MiRNA binding site number and density for circRNAs was calculated based on the TargetScan prediction performed by Circinteractome. CircRNA secondary structure prediction was calculated by their length normalized Gibbs free energy. All the statistical analysis were performed in Rstudio. Results The EV linear and circular transcriptome of MS patients and controls is characterized and compared to the transcriptome previously described in leucocytes. Results reveal differences in the RNA type distribution, showing that circRNAs are enriched in EVs compared to leucocytes. Nevertheless, highly structured circRNAs are preferentially retained in leukocytes. Additionally, differential expression analysis reports significant differences in circRNA and linear RNA expression between MS patients and controls as well as between different MS types. Conclusions The plasma derived EV RNA cargo is not a representation of leukocytes’ cytoplasm but a message that must be studied. Moreover, our results reveal the interest of circRNAs as part of this message highlighting the importance to further understand the RNA regulation in MS.

scholarly journals Association between age at onset of multiple sclerosis and vitamin D level in Saudi population

2019 ◽  
Vol 6 (9) ◽  
pp. 3728
Author(s):  
Hossam H. Younis ◽  
Abdulrahman H. Alzahrani ◽  
Abdulmageed S. Alomar
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Age At Onset ◽  
High Rate ◽  
Military Hospital ◽  
P Value ◽  
Healthy Controls ◽  
Saudi Population ◽  
Vitamin D Levels ◽  
Multiple Sclerosis Patients

Background: Several studies have shown an association between 25-hydroxyvitamin D (Vitamin D) levels and multiple sclerosis (MS). This study aimed to evaluate association between age at onset of Multiple Sclerosis and vitamin D level in Saudi population.Methods: This cross-sectional study was performed in the Neurology Department king Fahd Military Hospital Jeddah in the Kingdom of Saudi Arabia (KSA) included 75 patients with MS and 99 healthy controls group matched for gender and age. Comparing vitamin D measurement in multiple sclerosis patients at the time of diagnosis with healthy controls group.Results: We found no significant association between age at onset of multiple sclerosis and vitamin D level in Saudi population p value (0.723). However we also found that 74.66% of the sample Members who had MS and has a deficient of vitamin D and 83.83% people of the sample members didn’t have MS, but vitamin D was deficient with them.Conclusions: Study has revealed a high rate of vitamin D deficiency in patients with MS and in the controls group, as well Therese no clear relation to MS, Thus Therese no significant association between age at onset of multiple sclerosis and vitamin D level in Saudi population.

scholarly journals DNA methylation changes in glial cells of the normal-appearing white matter in Multiple Sclerosis patients

2021 ◽  
Author(s):  
Lara Kular ◽  
Ewoud Ewing ◽  
Maria Needhamsen ◽  
Majid Pahlevan Kakhki ◽  
Ruxandra Covacu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Dna Methylation ◽  
White Matter ◽  
Glial Cells ◽  
Treatment Options ◽  
Cell Types ◽  
P Value ◽  
Epigenetic Mark ◽  
Normal Appearing White Matter ◽  
Multiple Sclerosis Patients

Background Multiple Sclerosis (MS), the leading cause of non-traumatic neurological disability in young adults, is a chronic inflammatory and neurodegenerative disease of the central nervous system (CNS). Due to the poor accessibility to the target organ, CNS-confined processes underpinning the later progressive form of MS remain elusive thereby limiting treatment options. We aim to examine DNA methylation, a stable epigenetic mark of genome activity, in glial cells to capture relevant molecular changes underlying MS neuropathology. Methods We profiled DNA methylation in nuclei of glial cells, isolated from 38 post-mortem normal-appearing white matter (NAWM) specimens of MS patients (n=8) in comparison to white matter of control individuals (n=14), using Infinium MethylationEPIC BeadChip. Findings We identified 1,226 significant (genome-wide adjusted P-value < 0.05) differentially methylated positions (DMPs) between MS patients and controls. Functional annotation of the altered DMP-genes uncovered alterations of processes related to cellular motility, cytoskeleton dynamics, metabolic processes, synaptic support, neuroinflammation and signaling, such as Wnt and TGF-β pathways. A fraction of the affected genes displayed transcriptional differences in the brain of MS patients, as reported by publically available transcriptomic data. Cell type-restricted annotation of DMP-genes attributed alteration of cytoskeleton rearrangement and extracellular matrix remodelling to all glial cell types, while some processes, including ion transport, Wnt/TGF-β signaling and immune processes were more specifically linked to oligodendrocytes, astrocytes and microglial cells, respectively. Conclusion Our findings strongly suggest that NAWM glial cells are highly altered, even in the absence of lesional insult, collectively exhibiting a multicellular reaction in response to diffuse inflammation.

TNF-alpha Production by Peripheral Blood Monocytes in Multiple Sclerosis Patients and Healthy Controls

2015 ◽  
Vol 44 (6) ◽  
pp. 590-601 ◽  
Author(s):  
Mehrdad Farrokhi ◽  
Masoud Etemadifar ◽  
Maryam Sadat Jafary Alavi ◽  
Sayyed Hamid Zarkesh-Esfahani ◽  
Mohaddeseh Behjati ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Peripheral Blood ◽  
Tnf Alpha ◽  
Healthy Controls ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Alpha Production ◽  
Multiple Sclerosis Patients

CRYAB modulates the activation of CD4+ T cells from relapsing–remitting multiple sclerosis patients

2013 ◽  
Vol 19 (14) ◽  
pp. 1867-1877 ◽  
Author(s):  
Que Lan Quach ◽  
Luanne M Metz ◽  
Jenna C Thomas ◽  
Jonathan B Rothbard ◽  
Lawrence Steinman ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
Cytokine Production ◽  
Clinical Signs ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis

Background: Suppression of activation of pathogenic CD4+ T cells is a potential therapeutic intervention in multiple sclerosis (MS). We previously showed that a small heat shock protein, CRYAB, reduced T cell proliferation, pro-inflammatory cytokine production and clinical signs of experimental allergic encephalomyelitis, a model of MS. Objective: We assessed whether the ability of CRYAB to reduce the activation of T cells translated to the human disease. Methods: CD4+ T cells from healthy controls and volunteers with MS were activated in vitro in the presence or absence of a CRYAB peptide (residues 73–92). Parameters of activation (proliferation rate, cytokine secretion) and tolerance (anergy, activation-induced cell death, microRNAs) were evaluated. Results: The secretion of pro-inflammatory cytokines by CD4+ T cells was decreased in the presence of CRYAB in a subset of relapsing–remitting multiple sclerosis (RRMS) participants with mild disease severity while no changes were observed in healthy controls. Further, there was a correlation for higher levels of miR181a microRNA, a marker upregulated in tolerant CD8+ T cells, in CD4+ T cells of MS patients that displayed suppressed cytokine production (responders). Conclusion: CRYAB may be capable of suppressing the activation of CD4+ T cells from a subset of RRMS patients who appear to have less disability but similar age and disease duration.

Characterization of Th17 cells in multiple sclerosis patients and healthy controls

2014 ◽  
Vol 275 (1-2) ◽  
pp. 140-141
Author(s):  
Ulrike Bühler ◽  
René Gollan ◽  
Patrick Belikan ◽  
Frauke Zipp ◽  
Volker Siffrin
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cells ◽  
Healthy Controls ◽  
Multiple Sclerosis Patients

scholarly journals Monitoring cognitive change in multiple sclerosis using a computerized cognitive battery

2018 ◽  
Vol 4 (4) ◽  
pp. 205521731881551 ◽  
Author(s):  
L De Meijer ◽  
D Merlo ◽  
O Skibina ◽  
EJ Grobbee ◽  
J Gale ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cognitive Change ◽  
Progressive Multiple Sclerosis ◽  
Healthy Controls ◽  
Relapsing Remitting ◽  
Remitting Multiple Sclerosis ◽  
Serial Addition ◽  
Multiple Sclerosis Patients ◽  
Relapsing Remitting Multiple Sclerosis ◽  
Cognitive Monitoring

Background Cognitive monitoring that can detect short-term change in multiple sclerosis is challenging. Computerized cognitive batteries such as the CogState Brief Battery can rapidly assess commonly affected cognitive domains. Objectives The purpose of this study was to establish the acceptability and sensitivity of the CogState Brief Battery in multiple sclerosis patients compared to controls. We compared the sensitivity of the CogState Brief Battery to that of the Paced Auditory Serial Addition Test over 12 months. Methods Demographics, Expanded Disability Status Scale scores, depression and anxiety scores were compared with CogState Brief Battery and Paced Auditory Serial Addition Test performances of 51 patients with relapsing–remitting multiple sclerosis, 19 with secondary progressive multiple sclerosis and 40 healthy controls. Longitudinal data in 37 relapsing–remitting multiple sclerosis patients were evaluated using linear mixed models. Results Both the CogState Brief Battery and the Paced Auditory Serial Addition Test discriminated between multiple sclerosis and healthy controls at baseline ( p<0.001). CogState Brief Battery tasks were more acceptable and caused less anxiety than the Paced Auditory Serial Addition Test ( p<0.001). In relapsing–remitting multiple sclerosis patients, reaction time slowed over 12 months ( p<0.001) for the CogState Brief Battery Detection (mean change –34.23 ms) and Identification (–25.31 ms) tasks. Paced Auditory Serial Addition Test scores did not change over this time. Conclusions The CogState Brief Battery is highly acceptable and better able to detect cognitive change than the Paced Auditory Serial Addition Test. The CogState Brief Battery could potentially be used as a practical cognitive monitoring tool in the multiple sclerosis clinic setting.

T cell response to two immunodominant proteolipid protein (PLP) peptides in multiple sclerosis patients and healthy controls

1996 ◽  
Vol 1 (5) ◽  
pp. 270-278 ◽  
Author(s):  
CM Pelfrey ◽  
LR Tranquill ◽  
AB Vogt ◽  
HF McFarland
Keyword(s):  
Multiple Sclerosis ◽  
T Cell ◽  
Demyelinating Disease ◽  
T Cell Responses ◽  
Proteolipid Protein ◽  
T Cell Response ◽  
Healthy Controls ◽  
Cell Responses ◽  
Hla Binding ◽  
Multiple Sclerosis Patients

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system in which autoimmune T lymphocytes reacting with myelin antigens are believed to play a pathogenic role. Since HLA binding is involved in the selection of T cell responses, we have examined PLP peptide binding to HLA DR2, an HLA allele frequently found in MS patients. Both PLP 40–60 and PLP 89–106 show significant, high affinity binding to HLA DR2. We then tested whether responses to PLP peptides 40–60 and 89–106 are elevated in multiple sclerosis patients compared to matched controls. We also analysed T cell responses to MBP 87–106, which is considered to be the immunodominant region of MBP in humans. Here we demonstrate heterogenous T cell responses to PLP 40–60, PLP 89–106 and MBP 87–106 in both MS patients and controls. The overall number of TCL and the HLA restriction of those TCL did not vary significantly in the two groups. PLP 40–60 specific cytolytic TCL were increased in MS patients, whereas healthy controls had increased percentages of cytolytic TCL responding to PLP 89–106 and MBP 87–106. Although the data presented here shows heterogenous responses in T cell numbers, differences in numbers and specificity of cytolytic cells could be involved in the pathogenesis of autoimmune demyelinating disease.

Correlation between vitamin D and lipid profile in multiple sclerosis patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Azza AbdelNaser AbdelAziz ◽  
Prof Dr. Rasha Mamdouh Saleh ◽  
Mahmoud Saad Swelam ◽  
Janet Masoud Ayad
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Disease Activity ◽  
Lipid Profile ◽  
Serum Vitamin ◽  
Density Lipoprotein ◽  
P Value ◽  
Serum Vitamin D ◽  
The Mean ◽  
Multiple Sclerosis Patients

Abstract Background Studies have suggested that vitamin D and lipid profile have been linked to the etiology of multiple sclerosis and have an impact on the activity and progression of the disease. Objectives The aim of the present study was to determine correlation between vitamin D level and lipid profile in multiple sclerosis (MS) patients and their effect on disease activity and progression for better management and control of risk factors. Patients and Methods It is a cross-sectional hospital based study carried on clinically definite 111 Relapsing Remitting MS (RRMS) patients according to McDonald criteria 2010 recruited from Multiple sclerosis unit at Ain Shams University Hospitals, both genders included and aged from 18 to 50 years old. All subjects were assessed regarding their basic demographic data, serum vitamin D level and lipid profile and correlated these data with their state of disease activity and degree of disability. Results The mean level of serum vitamin D was 18.93 ± 9.85 ng/mL. Serum vitamin D level was insufficient (&lt; 30 ng/mL) in 81.08% of patients and sufficient (≥ 30 ng/mL) in 18.92% of patients. The mean level of total cholesterol (TC) was 204.9 ± 50.9 mg/dL, of tri-glycerides (TG) was 105.4 ± 44.6 mg/dL, of low density lipoprotein (LDL) was 122.2 ± 38.8 mg/dL and of high density lipoprotein (HDL) level was 56.2 ± 16.6 mg/dL. High relapse frequency was found to be significantly related to low serum vitamin D level with P-value 0.005. Near all lipid related variables were positively correlated to disease duration. TC and TG were positively related to EDSS while HDL was negatively related with it. Number of brain T2 lesions was significantly correlated with TC and TG levels with P-value 0.001 and 0.002 respectively. Fingolimod was found to be associated with dyslipidemia. We found that each 1 ng/mL increase in vitamin D was associated with decrease in TC of 1.48 mg/dL (95% CI: -2.42 to -0.54, P-value 0.002) and increase in HDL of 0.35 mg/dL (95% CI: 0.04 to -0.66, P-value 0.028). Conclusion Vitamin D deficiency is predominant among Egyptian MS patients. Patients with insufficient vitamin D were found to have higher annualized relapse rate (ARR). Patients with dyslipidemia found to have longer duration, more disability and higher brain T2 lesion load. Vitamin D was correlated positively with HDL and negatively with TC.

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