Multiple Sclerosis Patients In Response Research Articles

Disaster and Multiple Sclerosis: A Systematic Review.

Multiple Sclerosis (MS) patients experience a variety of disease caused disabilities that makes them more vulnerable to the effects of disasters. This study aimed to review all existed studies about disasters and related disaster management planning about MS patients. The PubMed, Google Scholar, Scopus, and Web of Science, ProQuest, science direct , and grey literature databases were searched up to the mid of 2021. All obtained titles were assessed by the inclusion criteria. Abstracts of the relevant titles were reviewed and eligible articles/documents were included for full text review and data abstraction. From 24616 Articles/documents, finally 15 documents (13 articles, and 2 books) were selected. In 8 articles (53%) specifically, focused on MS patients and, in the rest focused on them as a member of people with disabilities. Most studies (10, 71.4%), emphasized on the disaster induced stress effect on MS patients. In two books/book sections, the disaster preparedness plan for all types of disabilities was presented in general, and MS patients were mentioned as a member of the group of patients with disabilities. Despite the importance of planning in response to disasters to address specific problems of MS patients, there is a lack of proper planning. This is very important and there is an urgent need to develop appropriate planning protocols for addressing the special conditions of MS patients in response to disasters.

Serum Exosome MicroRNAs Predict Multiple Sclerosis Disease Activity after Fingolimod Treatment.

We and others have previously demonstrated the potential for circulating exosome microRNAs to aid in disease diagnosis. In this study, we sought the possible utility of serum exosome microRNAs as biomarkers for disease activity in multiple sclerosis patients in response to fingolimod therapy. We studied patients with relapsing-remitting multiple sclerosis prior to and 6months after treatment with fingolimod. Disease activity was determined using gadolinium-enhanced magnetic resonance imaging. Serum exosome microRNAs were profiled using next-generation sequencing. Data were analysed using univariate/multivariate modelling and machine learning to determine microRNA signatures with predictive utility. Accordingly, we identified 15 individual miRNAs that were differentially expressed in serum exosomes from post-treatment patients with active versus quiescent disease. The targets of these microRNAs clustered in ontologies related to the immune and nervous systems and signal transduction. While the power of individual microRNAs to predict disease status post-fingolimod was modest (average 77%, range 65 to 91%), several combinations of 2 or 3 miRNAs were able to distinguish active from quiescent disease with greater than 90% accuracy. Further stratification of patients identified additional microRNAs associated with stable remission, and a positive response to fingolimod in patients with active disease prior to treatment. Overall, these data underscore the value of serum exosome microRNA signatures as non-invasive biomarkers of disease in multiple sclerosis and suggest they may be used to predict response to fingolimod in future clinical practice. Additionally, these data suggest that fingolimod may have mechanisms of action beyond its known functions.

Combined exercise training reduces fatigue and modulates the cytokine profile of T-cells from multiple sclerosis patients in response to neuromediators

Fatigue is a common and disabling symptom of multiple sclerosis (MS), a classical Th1- and Th17-mediated autoimmune disease. There is no effective pharmacological treatment for fatigue, but some reports point towards beneficial effects of physical activity on management of the fatigue in MS patients. As both MS and fatigue have been associated with dysregulated cytokine network production, the objective of the present study was to evaluate the impact of a physical activity program consisting of a 12-week series of combining Pilates and aerobic exercises on fatigue severity, determined by FSS, and cytokine production, quantified by ELISA, by T cells from MS patients (n=08) with low disability (EDSS≤2). The results showed decrease in FSSs in all patients at the end of physical activity intervention. Regarding the cytokines, a significant reduction of IL-22 release was observed in polyclonally-activated T cells form MS patients post-training follow-up. Interestingly, while the physical activity attenuated the ability of dopamine in up-regulating Th17-related cytokines, it enhanced the anti-inflammatory effects of serotonin, evidenced by high IL-10 production. In summary, all results suggest that programmed physical activity has beneficial effects on management of fatigue in MS patients, and it could be related, at least in part, to its ability in regulating neuroimmune parameters into T cell compartment.

Activation of Type I Interferon Signal Pathway in Patients with Multiple Sclerosis by the Russian Analog of β-Interferon-1b (transcriptional profiling data)

The introduction of Russian analogs of β-interferon (β-IFN) produced by recombinant strains of E. coli (β-IFN-1b) into medical practice in Russia for the pathogenetic treatment of multiple sclerosis (MS) requires, in accordance with contemporary standards, confirmation by transcriptome analysis that they activate the main signal pathways involved in the mechanism of action of β-IFN. In the present report we present such an analysis for Infibeta (produced by Generium). Whole-genome transcription profiling using an Illumina HT-12 microarray was performed to identify genes showing differential expression in peripheral blood mononuclear cells from MS patients in response to exposure to this agent. Comparison of the levels of gene expression in MS patients not previously treated with any kind of immunomodulatory therapy before and 10 h after the first dose of agent identified 490 genes whose expression showed statistically significant changes, of which 191 genes showed increases in expression (up-regulated genes) and 299 genes showed decreases in expression (down-regulated genes). These genes included genes from the inflammation system, the innate and adaptive immune systems, apoptosis, signal transmission, transcription, translation, and degradation. Analysis of the overall expression of sets (groups) of genes (gene set analysis) yielded data which may provide evidence that IFN type I signal pathway genes, as well as IFN-induced genes, are involved in patients’ responses to the agent. Thus, analysis by transcriptional profiling led to the conclusion that the mechanism of the immunomodulatory action of Infibeta is identical to that described for original β-IFN formulations.

The neurotransmitter glutamate and human T cells: glutamate receptors and glutamate-induced direct and potent effects on normal human T cells, cancerous human leukemia and lymphoma T cells, and autoimmune human T cells

Glutamate is the most important excitatory neurotransmitter of the nervous system, critically needed for the brain's development and function. Glutamate has also a signaling role in peripheral organs. Herein, we discuss glutamate receptors (GluRs) and glutamate-induced direct effects on human T cells. T cells are the most important cells of the adaptive immune system, crucially needed for eradication of all infectious organisms and cancer. Normal, cancer and autoimmune human T cells express functional ionotropic and metabotropic GluRs. Different GluR subtypes are expressed in different T cell subtypes, and in resting vs. activated T cells. Glutamate by itself, at low physiological 10(-8)M to 10(-5)M concentrations and via its several types of GluRs, activates many key T cell functions in normal human T cells, among them adhesion, migration, proliferation, intracellular Ca(2+) fluxes, outward K(+) currents and more. Glutamate also protects activated T cells from antigen-induced apoptotic cell death. By doing all that, glutamate can improve substantially the function and survival of resting and activated human T cells. Yet, glutamate's direct effects on T cells depend dramatically on its concentration and might be inhibitory at excess pathological 10(-3)M glutamate concentrations. The effects of glutamate on T cells also depend on the specific GluRs types expressed on the target T cells, the T cell's type and subtype, the T cell's resting or activated state, and the presence or absence of other simultaneous stimuli besides glutamate. Glutamate also seems to play an active role in T cell diseases. For example, glutamate at several concentrations induces or enhances significantly very important functions of human T-leukemia and T-lymphoma cells, among them adhesion to the extracellular matrix, migration, in vivo engraftment into solid organs, and the production and secretion of the cancer-associated matrix metalloproteinase MMP-9 and its inducer CD147. Glutamate induces all these effects via activation of GluRs highly expressed in human T-leukemia and T-lymphoma cells. Glutamate also affects T cell-mediated autoimmune diseases. With regards to multiple sclerosis (MS), GluR3 is highly expressed in T cells of MS patients, and upregulated significantly during relapse and when there is neurological evidence of disease activity. Moreover, glutamate or AMPA (10(-8)M to 10(-5)M) enhances the proliferation of autoreactive T cells of MS patients in response to myelin proteins. Thus, glutamate may play an active role in MS. Glutamate and its receptors also seem to be involved in autoimmune rheumatoid arthritis and systemic lupus erythematosus. Finally, T cells can produce and release glutamate that in turn affects other cells, and during the contact between T cells and dendritic cells, the latter cells release glutamate that has potent effects on the T cells. Together, these evidences show that glutamate has very potent effects on normal, and also on cancer and autoimmune pathological T cells. Moreover, these evidences suggest that glutamate and glutamate-receptor agonists might be used for inducing and boosting beneficial T cell functions, for example, T cell activity against cancer and infectious organisms, and that glutamate-receptor antagonists might be used for preventing glutamate-induced activating effects on detrimental autoimmune and cancerous T cells.

Altered innate immune response of plasmacytoid dendritic cells in multiple sclerosis

Plasmacytoid dendritic cells (pDCs) are of crucial importance in immune regulation and response to microbial factors. In multiple sclerosis (MS), pDCs from peripheral blood showed an immature phenotype, but its role in susceptibility to MS is not determined. Because infectious diseases are established triggers of exacerbations in MS, in this study we have characterized the expression of Toll-like receptors (TLR) and the maturation and functional properties of peripheral blood pDCs from clinically stable, untreated MS patients in response to signals of innate immunity. After stimulation of TLR-9, interferon (IFN)-alpha production by pDCs was significantly lower in MS (n = 12) compared to healthy controls (n = 9). In an allogenic two-step co-culture assay we found an impaired effect of TLR-9 stimulation on IFN-gamma expression of autologous naive T cells in MS patients (n = 4). In peripheral blood mononuclear cells, TLR-9 stimulation with type A CpG ODN resulted in a higher expression of TLR-1, -2, -4, -5 and -8 in MS patients (n = 7) compared with healthy controls (n = 11). These findings suggest an altered innate immune response to microbial stimuli in MS patients and may help understanding of why common infectious agents trigger MS attacks.