scholarly journals No differential gene expression for CD4+ T cells of MS patients and healthy controls

2019 ◽  
Vol 5 (2) ◽  
pp. 205521731985690 ◽  
Author(s):  
Ina S Brorson ◽  
Anna Eriksson ◽  
Ingvild S Leikfoss ◽  
Elisabeth G Celius ◽  
Pål Berg-Hansen ◽  
...  

Background Multiple sclerosis-associated genetic variants indicate that the adaptive immune system plays an important role in the risk of developing multiple sclerosis. It is currently not well understood how these multiple sclerosis-associated genetic variants contribute to multiple sclerosis risk. CD4+ T cells are suggested to be involved in multiple sclerosis disease processes. Objective We aim to identify CD4+ T cell differential gene expression between multiple sclerosis patients and healthy controls in order to understand better the role of these cells in multiple sclerosis. Methods We applied RNA sequencing on CD4+ T cells from multiple sclerosis patients and healthy controls. Results We did not identify significantly differentially expressed genes in CD4+ T cells from multiple sclerosis patients. Furthermore, pathway analyses did not identify enrichment for specific pathways in multiple sclerosis. When we investigated genes near multiple sclerosis-associated genetic variants, we did not observe significant enrichment of differentially expressed genes. Conclusion We conclude that CD4+ T cells from multiple sclerosis patients do not show significant differential gene expression. Therefore, gene expression studies of all circulating CD4+ T cells may not result in viable biomarkers. Gene expression studies of more specific subsets of CD4+ T cells remain justified to understand better which CD4+ T cell subsets contribute to multiple sclerosis pathology.

2020 ◽  
Vol 6 (4) ◽  
pp. 205521732097851
Author(s):  
IS Brorson ◽  
AM Eriksson ◽  
IS Leikfoss ◽  
V Vitelli ◽  
EG Celius ◽  
...  

Background Genetic and clinical observations have indicated T cells are involved in MS pathology. There is little insight in how T cells are involved and whether or not these can be used as markers for MS. Objectives Analysis of the gene expression profiles of circulating CD8+ T cells of MS patients compared to healthy controls. Methods RNA from purified CD8+ T cells was sequenced and analyzed for differential gene expression. Pathway analyses of genes at several p-value cutoffs were performed to identify putative pathways involved. Results We identified 36 genes with significant differential gene expression in MS patients. Four genes reached at least 2-fold differences in expression. The majority of differentially expressed genes was higher expressed in MS patients. Genes associated to MS in GWAS showed enrichment amongst the differentially expressed genes. We did not identify enrichment of specific pathways amongst the differentially expressed genes in MS patients. Conclusions CD8+ T cells of MS patients show differential gene expression, with predominantly higher activity of genes in MS patients. We do not identify specific biological pathways in our study. More detailed analysis of CD8+ T cells and subtypes of these may increase understanding of how T cells are involved in MS.


2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Mohammad Javad Tavassolifar ◽  
Abdorreza Naser Moghadasi ◽  
Behnaz Esmaeili ◽  
Omid Sadatpour ◽  
Mohammad Vodjgani ◽  
...  

As a prevalent autoimmune disease of the central nervous system in young adults, multiple sclerosis (MS) is mediated by T cells, particularly CD4+ subsets. Given the evidence that the perturbation in reactive oxygen species (ROS) production has a pivotal role in the onset and progression of MS, its regulation through the antioxidant molecules is too important. Here, we investigated the level of the redox system components in lymphocytes and CD4+ T cells of MS patients. The study was performed on relapsing-remitting MS (RRMS) patients ( n = 29 ) and age- and sex-matched healthy controls ( n = 15 ). Peripheral blood mononuclear cells (PBMCs) were cultured and stimulated by anti-CD3/CD28. The level of ROS, anion superoxide (O2-), and L-𝛾-glutamyl-Lcysteinylglycine (GSH) was measured by flow cytometry in lymphocytes/CD4+ T cells. The gene expression level of gp91phox, catalase, superoxide dismutase 1/2 (SOD), and nuclear factor-E2-related factor (Nrf2) was also measured by real-time PCR. We found that lymphocytes/CD4+ T cells of RRMS patients at the relapse phase significantly produced higher levels of ROS and O2- compared to patients at the remission phase ( P value < 0.001) and healthy controls ( P value < 0.001 and P value < 0.05, respectively). Interestingly, the gene expression level of gp91phox, known as the catalytic subunit of the NADPH oxidase, significantly increased in MS patients at the relapse phase ( P value < 0.05). Furthermore, the catalase expression augmented in patients at the acute phase ( P value < 0.05), while an increased expression of SOD1 and Nrf2 was found in RRMS patients at relapse and remission phases ( P value < 0.05). The increased production of ROS in CD4+ T cells of RRMS patients highlights the importance of amplifying antioxidant components as an efficient approach to ameliorate disease activity in MS patients.


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