scholarly journals Identification of key genes associated with multiple sclerosis based on gene expression data from peripheral blood mononuclear cells

PeerJ ◽  
2020 ◽  
Vol 8 ◽  
pp. e8357 ◽  
Author(s):  
Zhenwei Shang ◽  
Wenjing Sun ◽  
Mingming Zhang ◽  
Lidan Xu ◽  
Xueyuan Jia ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Candidate Genes ◽  
Mononuclear Cells ◽  
Biological Processes ◽  
Peripheral Blood Mononuclear ◽  
Protein Protein Interaction ◽  
Microarray Expression ◽  
Disease Pathways ◽  
Combined Data

The aim of this study was to identify the potential key candidate genes of multiple sclerosis (MS) and uncover mechanisms in MS. We combined data from the microarray expression profile of three MS stages and performed bioinformatics analysis. Differentially expressed genes (DEGs) were identified among the distinct stages of MS and healthy controls, and a total of 349 shared DEGs were identified. Gene ontology (GO) and pathway enrichment analyses showed that the DEGs were significantly enriched in the biological processes (BPs) of purine-related metabolic processes and signaling, especially the common DEGs, which were enriched in some immunological processes. Most of the DEGs were enriched in signaling pathways associated with the immune system, some immune diseases and infectious disease pathways. Through a protein–protein interaction (PPI) network analysis and a gene expression regulatory network constructed with MS-related miRNAs, we confirmed FOS, TP53, VEGFA, JUN, HIF1A, RB1, PTGS2, CXCL8, OAS2, NFKBIA and OAS1 as candidate genes of MS. Furthermore , we explored the potential SNPs associated with MS by database mining. In conclusion, this study provides the identified genes, SNPs, biological processes, and cellular pathways associated with MS. The uncovered candidate genes may be potential biomarkers involved in the diagnosis and therapy of MS.

scholarly journals Gene expression of chemokines CX3CL1 and CXCL16 and their receptors, CX3CR1 and CXCR6, in peripheral blood mononuclear cells of patients with relapsing-remitting multiple sclerosis - a pilot study

2020 ◽  
Vol 77 (9) ◽  
pp. 967-973
Author(s):  
Ljiljana Stojkovic ◽  
Aleksandra Stankovic ◽  
Ivan Zivotic ◽  
Evica Dincic ◽  
Dragan Alavantic ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Fold Change ◽  
Mrna Levels ◽  
Peripheral Blood Mononuclear ◽  
Relapsing Remitting ◽  
Blood Mononuclear Cells

Background/Aim. In vitro and in vivo studies show that CX3CL1 and CXCL16 chemokines and their specific receptors, CX3CR1 and CXCR6, respectively, mediate mechanism of neuroinflammation during the pathogenesis of multiple sclerosis (MS). The aim of this study was to investigate relative messenger ribonucleic acid (mRNA) levels of CX3CL1, CXCL16, CX3CR1 and CXCR6 in peripheral blood mononuclear cells, as potential molecular markers of relapsing-remitting (RR) MS. Methods. The study included 43 unrelated RR MS patients, 20 of them with clinically active disease (relapse) and 23 with clinically stable disease (remission), and 28 unrelated healthy subjects as controls. Real-time polymerase chain reactions (PCR) were performed using TaqMan? gene expression assays. Relative expression (mRNA) level of each target gene in each sample of peripheral blood mononuclear cells was calculated as the mean normalized expression. Results. The levels of CX3CR1 mRNA were significantly higher in clinically active RR MS patients compared to controls [fold change = 1.38, p (Mann-Whitney U test) = 0.009], and significantly lower in clinically stable vs active RR MS patients [fold change = - 1.43, p (t-test) = 0.03]. Stable RR MS patients had significantly higher CXCL16 mRNA levels than controls [fold change = 1.33, p (Mann-Whitney U test) = 0.006]. A trend of increased CXCR6 gene expression was found in active RR MS patients compared to controls [fold change = 1.23, p (Mann-Whitney U test) = 0.08]. In either active or stable RR MS patients there were no significant correlations of the clinical parameters with expression levels of the target genes. Conclusion. The current results show that increased CX3CR1 mRNA levels in peripheral blood mononuclear cells could represent a proinflammatory molecular marker of clinically active RR MS.

scholarly journals Combined Transcriptome and Proteome Leukocyte’s Profiling Reveals Up-Regulated Module of Genes/Proteins Related to Low Density Neutrophils and Impaired Transcription and Translation Processes in Clinical Sepsis

2021 ◽  
Vol 12 ◽  
Author(s):  
Giuseppe Gianini Figueirêdo Leite ◽  
Bianca Lima Ferreira ◽  
Alexandre Keiji Tashima ◽  
Erika Sayuri Nishiduka ◽  
Edecio Cunha-Neto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Interaction Network ◽  
Low Density ◽  
Mitochondrial Translation ◽  
Peripheral Blood Mononuclear ◽  
Protein Coding ◽  
Protein Protein Interaction ◽  
Network Analyses ◽  
Host Defense System

Sepsis is a global health emergency, which is caused by various sources of infection that lead to changes in gene expression, protein-coding, and metabolism. Advancements in “omics” technologies have provided valuable tools to unravel the mechanisms involved in the pathogenesis of this disease. In this study, we performed shotgun mass spectrometry in peripheral blood mononuclear cells (PBMC) from septic patients (N=24) and healthy controls (N=9) and combined these results with two public microarray leukocytes datasets. Through combination of transcriptome and proteome profiling, we identified 170 co‐differentially expressed genes/proteins. Among these, 122 genes/proteins displayed the same expression trend. Ingenuity Pathway Analysis revealed pathways related to lymphocyte functions with decreased status, and defense processes that were predicted to be strongly increased. Protein-protein interaction network analyses revealed two densely connected regions, which mainly included down‐regulated genes/proteins that were related to the transcription of RNA, translation of proteins, and mitochondrial translation. Additionally, we identified one module comprising of up‐regulated genes/proteins, which were mainly related to low-density neutrophils (LDNs). LDNs were reported in sepsis and in COVID-19. Changes in gene expression level were validated using quantitative real-time PCR in PBMCs from patients with sepsis. To further support that the source of the upregulated module of genes/proteins found in our results were derived from LDNs, we identified an increase of this population by flow cytometry in PBMC samples obtained from the same cohort of septic patients included in the proteomic analysis. This study provides new insights into a reprioritization of biological functions in response to sepsis that involved a transcriptional and translational shutdown of genes/proteins, with exception of a set of genes/proteins related to LDNs and host‐defense system.

scholarly journals Understanding Autoimmune Mechanisms in Multiple Sclerosis Using Gene Expression Microarrays: Treatment Effect and Cytokine-related Pathways

2004 ◽  
Vol 11 (3-4) ◽  
pp. 299-305 ◽  
Author(s):  
A. Achiron ◽  
M. Gurevich ◽  
D. Magalashvili ◽  
I. Kishner ◽  
M. Dolev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Treatment Effects ◽  
Mononuclear Cells ◽  
Gene Expression Signature ◽  
Immunomodulatory Treatment ◽  
Peripheral Blood Mononuclear ◽  
Expression Signature ◽  
Gene Expression Microarrays ◽  
Expression Microarrays

Multiple sclerosis (MS) is a central nervous system disease in which activated autoreactive T-cells invade the blood brain barrier and initiate an inflammatory response that leads to myelin destruction and axonal loss. The etiology of MS, as well as the mechanisms associated with its unexpected onset, the unpredictable clinical course spanning decades, and the different rates of progression leading to disability over time, remains an enigma. We have applied gene expression microarrays technology in peripheral blood mononuclear cells (PBMC) to better understand MS pathogenesis and better target treatment approaches. A signature of 535 genes were found to distinguish immunomodulatory treatment effects between 13 treated and 13 untreated MS patients. In addition, the expression pattern of 1109 gene transcripts that were previously reported to significantly differentiate between MS patients and healthy subjects were further analyzed to study the effect of cytokine-related pathways on disease pathogenesis. When relative gene expression for 26 MS patients was compared to 18 healthy controls, 30 genes related to various cytokine-associated pathways were identified. These genes belong to a variety of families such as interleukins, small inducible cytokine subfamily and tumor necrosis factor ligand and receptor. Further analysis disclosed seven cytokine-associated genes within the immunomodulatory treatment signature, and two cytokine-associated genes SCYA4 (small inducible cytokine A4) and FCAR (Fc fragment of IgA, CD89) that were common to both the MS gene expression signature and the immunomodulatory treatment gene expression signature. Our results indicate that cytokine-associated genes are involved in various pathogenic pathways in MS and also related to immunomodulatory treatment effects.

scholarly journals Evaluation of the Effect of Epigallocatechin-3-gallate (EGCG) on HIF-1α Protein and RORC Gene Expression in Peripheral Blood Mononuclear Cells of Patients with Multiple Sclerosis

2021 ◽  
Author(s):  
Freshteh Alsahebfosoul ◽  
◽  
Boshra Afshar ◽  
Mazdak Ganjalikhani-Hakemi ◽  
Zahra Khalifezadeh Esfahani ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Th17 Cells ◽  
Mononuclear Cells ◽  
Enzyme Linked Immunosorbent Assay ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Anti Inflammatory

Background: Multiple sclerosis has been considered as chronic inflammation of the central nervous system (CNS) and autoimmune disease .MS is most widely considered to be mediated by activation of myelin-specific T CD4+ cells as well as TH1 and TH17 cells. TH17 cell has been involved in the pathogenesis of MS in various ways. HIF-1α and RORC are required for natural differentiation of TH17 and are essential transcription factors for the evolution of TH17 cells. Numerous studies indicate that epigallocatechin gallate (EGCG) has immunomodulatory and anti-inflammatory effects. Aims: This study investigated the effect of EGCG on normoxic HIF-1α and RORC2 expression in PBMCs of MS patients. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood of new cases MS patients. The cells cultured in the presence of a different concentration of EGCG (25, 50,100μM) for 18 and 48 hours. Afterward, HIF-1α and RORC2 level expressions were measured by enzyme-linked immunosorbent assay (ELISA) and Real-Time PCR, respectively. Result: The results showed that EGCG significantly decrease RORC2 gene expression. However, EGCG did not influence the level of HIF-1α. Our present data has led us to conclude that EGCG could be considered as an anti-inflammatory agent may serving as an achievable therapeutic agent for MS.

Gene expression analysis of relapsing–remitting, primary progressive and secondary progressive multiple sclerosis

2013 ◽  
Vol 19 (14) ◽  
pp. 1841-1848 ◽  
Author(s):  
R Ratzer ◽  
HB Søndergaard ◽  
J Romme Christensen ◽  
L Börnsen ◽  
R Borup ◽  
...  
Keyword(s):  
Gene Expression ◽  
Multiple Sclerosis ◽  
T Cells ◽  
B Cells ◽  
Cd8 T Cells ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Primary Progressive ◽  
Secondary Progressive ◽  
Relapsing Remitting

Background: Previous studies of multiple sclerosis (MS) have indicated differences in the pathogenesis in relapsing–remitting (RRMS), secondary progressive (SPMS) and primary progressive (PPMS) disease. Objective: We hypothesized that different MS subtypes would show differences in gene expression that could be traced to specific subsets of peripheral blood mononuclear cells (PBMCs). Methods: Gene expression in RRMS, SPMS, PPMS and healthy control (HC) PBMCs was analyzed on Affymetrix arrays. In addition, we studied gene expression in pools of purified PBMC subsets. Results: We found 380 genes that were differentially expressed in RRMS, PPMS, SPMS and HCs (false discovery rate < 5%). There were no major differences between the subtypes of MS. The genes showing most prominent expression changes in RRMS were associated with adaptive immune pathways, while genes in PPMS were associated with innate immune system pathways. SPMS patients shared pathways with RRMS and PPMS patients. Gene expression changes were most prominent in B cells, CD8+ T cells and monocytes. Conclusion: Differences in gene expression, which could be traced to B cells, CD8+ T cells and monocytes, were found between MS patients and HCs but only minor differences were observed between MS subgroups.

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