The 795CT polymorphism in osteopontin gene is not associated with multiple sclerosis in a Spanish population

2007 ◽  
Vol 13 (2) ◽  
pp. 250-252 ◽  
Author(s):  
A Mas ◽  
A Martínez ◽  
V De Las Heras ◽  
M Bartolomé ◽  
Eg De La Concha ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Interleukin 10 ◽  
Interleukin 12 ◽  
Italian Population ◽  
Cytokine Network ◽  
Activated T Cells ◽  
Negative Finding ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an inflammatory disease affecting the central nervous system. The dysregulation of the cytokine network is an important component of its pathogenesis. One of the cytokines produced by activated T-cells is osteopontin (OPN). OPN enhances the production of the pro-inflammatory cytokines, interleukin-12 and interferon-gamma, while reducing interleukin-10 levels. Therefore, OPN is considered a pro-inflammatory cytokine, and could play a key role in MS pathogenesis. The OPN gene contains several common polymorphisms, distributed in two main haplotypes, which may modulate its production or activity. A total of 326 MS patients and 484 healthy controls were typed for 795CT OPN polymorphism. In order to perform a familial study, 51 progenitor pairs were also included. No difference was found in the case-control or family study. This negative finding is inconsistent with a previous haplotype study in an Italian population, where the haplotype associated carried the low-frequency allele in position 795. In a Japanese population, a similar study yielded no association with this polymorphism. In conclusion, our data suggest that the 795 polymorphism does not play an etiological role per se and the haplotype structure may differ from one population to another. Multiple Sclerosis 2007; 13: 250–252. http://msj.sagepub.com

scholarly journals Multiple Sclerosis and Obesity: Possible Roles of Adipokines

2016 ◽  
Vol 2016 ◽  
pp. 1-24 ◽  
Author(s):  
José de Jesús Guerrero-García ◽  
Lucrecia Carrera-Quintanar ◽  
Rocío Ivette López-Roa ◽  
Ana Laura Márquez-Aguirre ◽  
Argelia Esperanza Rojas-Mayorquín ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Early Life ◽  
Neural Tissue ◽  
Autoimmune Disorder ◽  
Susceptibility Factor ◽  
Related Risk ◽  
Inflammatory State ◽  
The Central Nervous System ◽  
Ms Pathogenesis

Multiple Sclerosis (MS) is an autoimmune disorder of the Central Nervous System that has been associated with several environmental factors, such as diet and obesity. The possible link between MS and obesity has become more interesting in recent years since the discovery of the remarkable properties of adipose tissue. Once MS is initiated, obesity can contribute to increased disease severity by negatively influencing disease progress and treatment response, but, also, obesity in early life is highly relevant as a susceptibility factor and causally related risk for late MS development. The aim of this review was to discuss recent evidence about the link between obesity, as a chronic inflammatory state, and the pathogenesis of MS as a chronic autoimmune and inflammatory disease. First, we describe the main cells involved in MS pathogenesis, both from neural tissue and from the immune system, and including a new participant, the adipocyte, focusing on their roles in MS. Second, we concentrate on the role of several adipokines that are able to participate in the mediation of the immune response in MS and on the possible cross talk between the latter. Finally, we explore recent therapy that involves the transplantation of adipocyte precursor cells for the treatment of MS.

Oligoclonal IgGs against DNA, Histones, and Myelin Basic Protein in the Cerebrospinal Fluid of Patients with Multiple Sclerosis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kostrikina IA ◽  
◽  
Granieri E ◽  
Nevinsky GA ◽  
◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cerebrospinal Fluid ◽  
Myelin Basic Protein ◽  
Basic Protein ◽  
Main Role ◽  
Barr Virus ◽  
The Central Nervous System ◽  
Epstein Barr ◽  
Ms Pathogenesis ◽  
Myelin Proteolipid

Multiple Sclerosis (MS) is known as a chronic demyelinating pathology of the central nervous system. The most accepted MS pathogenesis theory assigns the main role to demyelination of myelin-proteolipid shells due to inflammationrelated with autoimmune reactions. One of the features of MS patients is the enhanced synthesis of oligoclonal IgGs in the bone marrow Cerebrospinal Fluid (CSF). By antigen-specific immunoblotting after isoelectrofocusing of IgGs, oligoclonal IgGs in CSF of MS patients were revealed only against the components of Epstein-Barr virus and Chlamydia. However, there was still unknown to which human auto-antigens in MS patients oligoclonal IgGs may be produced. Here it was first shown that in the CSF of a narrow percentage of MS patients, oligoclonal IgGs are produced against their own antigens: DNA (24% patients), histones (20%), and myelin basic protein (12%). At the same time, the CSF of MS patients contains a very large amount of auto-IgGs-abzymes that hydrolyze DNA, histones, and myelin basic protein, which during isofocusing, are distributed throughout the gel from pH 3 to 10. It is concluded that these multiple IgGs-abzymes, which are dangerous to humans since stimulate development of MS, in the main are non-oligoclonal antibodies.

scholarly journals Potential Impact of B Cells on T Cell Function in Multiple Sclerosis

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Sara Ireland ◽  
Nancy Monson
Keyword(s):  
Multiple Sclerosis ◽  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Function ◽  
The Central Nervous System ◽  
Potential Impact ◽  
Anti Cd20 ◽  
The Impact ◽  
Ms Pathogenesis

Multiple sclerosis is a chronic debilitating autoimmune disease of the central nervous system. The contribution of B cells in the pathoetiology of MS has recently been highlighted by the emergence of rituximab, an anti-CD20 monoclonal antibody that specifically depletes B cells, as a potent immunomodulatory therapy for the treatment of MS. However, a clearer understanding of the impact B cells have on the neuro-inflammatory component of MS pathogenesis is needed in order to develop novel therapeutics whose affects on B cells would be beneficial and not harmful. Since T cells are known mediators of the pathology of MS, the goal of this review is to summarize what is known about the interactions between B cells and T cells, and how current and emerging immunotherapies may impact B-T cell interactions in MS.

scholarly journals Engine Failure in Axo-Myelinic Signaling: A Potential Key Player in the Pathogenesis of Multiple Sclerosis

2021 ◽  
Vol 15 ◽  
Author(s):  
Talia Bergaglio ◽  
Antonio Luchicchi ◽  
Geert J. Schenk
Keyword(s):  
Multiple Sclerosis ◽  
Tissue Injury ◽  
Neuronal Loss ◽  
Glia Cells ◽  
Inflammatory Processes ◽  
The Central Nervous System ◽  
Triggering Mechanisms ◽  
Engine Failure ◽  
Inside Out ◽  
Ms Pathogenesis

Multiple Sclerosis (MS) is a complex and chronic disease of the central nervous system (CNS), characterized by both degenerative and inflammatory processes leading to axonal damage, demyelination, and neuronal loss. In the last decade, the traditional outside-in standpoint on MS pathogenesis, which identifies a primary autoimmune inflammatory etiology, has been challenged by a complementary inside-out theory. By focusing on the degenerative processes of MS, the axo-myelinic system may reveal new insights into the disease triggering mechanisms. Oxidative stress (OS) has been widely described as one of the means driving tissue injury in neurodegenerative disorders, including MS. Axonal mitochondria constitute the main energy source for electrically active axons and neurons and are largely vulnerable to oxidative injury. Consequently, axonal mitochondrial dysfunction might impair efficient axo-glial communication, which could, in turn, affect axonal integrity and the maintenance of axonal, neuronal, and synaptic signaling. In this review article, we argue that OS-derived mitochondrial impairment may underline the dysfunctional relationship between axons and their supportive glia cells, specifically oligodendrocytes and that this mechanism is implicated in the development of a primary cytodegeneration and a secondary pro-inflammatory response (inside-out), which in turn, together with a variably primed host’s immune system, may lead to the onset of MS and its different subtypes.

scholarly journals Vitamins a and D Enhance the Expression of Ror-γ-Targeting MiRNAs in a Mouse Model of Multiple Sclerosis

2021 ◽  
Author(s):  
Marziyeh Mohammadi kordkhayli ◽  
Mohammd Ali Sahraian ◽  
Samira Ghorbani ◽  
Fatemeh Mansuri ◽  
Farideh Talebi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Th17 Cells ◽  
Protective Role ◽  
Rt Pcr ◽  
Strong Negative Correlation ◽  
The Central Nervous System ◽  
Mirnas Expression ◽  
Ms Pathogenesis ◽  
Lower Expression

Abstract Background: Multiple Sclerosis (MS) is an autoimmune disease of the central nervous system. Autoreactive T cells including cells with a Th17 phenotype are critical players in MS pathogenesis. In this study, we investigated the effects of VitA/D on miRNAs expression involved in Th17 development neuroinflammation using (EAE). Methods: EAE was induced in C57BL/6 mice and received IP injections of vitamins A, D or their combination starting one day before the immunization and continued every other day for 30 days. Animals were scored for 30 days. Percentages of Th17 cells were measured in splenocytes following in vitro re-stimulation with MOG using intracellular staining and flow cytometry. Expression of miR-98-5p and Let-7a-5p, two miRNAs that are known to target Ror-t and Ror-t was measured in MOG-stimulated splenocytes as well as in spinal cord tissues using real-time RT-PCR. Results: Treated mice showed decreased frequency of Th17 cells in their spleens following in vitro re-stimulation with antigen, also lower expression of IL17 and Ror-t in their in CNS and splenocytes. Vitamin A and vitamin D-treated splenocytes showed significant upregulation of miR-98-5p in 24 hour and 48 hours time-points and Let-7a-5p expression was induced at 48-hour post-treatment in MOG-treated cells, which showed a strong negative correlation with splenocyte Ror-t levels. Conclusion: Our data suggest that treatment with vitamins A and D can decreased differentiation of Th17 phenotype. This is likely due to upregulation of Ror-t-targeting miRNAs, miR-98-5p and Let-7a-5p following treatment. These findings point to a potential protective role for miRNAs in the context of autoimmune neuroinflammation.

scholarly journals Non-coding RNAs in the Pathogenesis of Multiple Sclerosis

2021 ◽  
Vol 12 ◽  
Author(s):  
Aadil Yousuf ◽  
Abrar Qurashi
Keyword(s):  
Multiple Sclerosis ◽  
Axonal Loss ◽  
Biological Processes ◽  
Protein Coding ◽  
The Past ◽  
The Central Nervous System ◽  
Non Coding Rnas ◽  
Genetic And Environmental Factors ◽  
Ms Pathogenesis

Multiple sclerosis (MS) is an early onset chronic neurological condition in adults characterized by inflammation, demyelination, gliosis, and axonal loss in the central nervous system. The pathological cause of MS is complex and includes both genetic and environmental factors. Non-protein-coding RNAs (ncRNAs), specifically miRNAs and lncRNAs, are important regulators of various biological processes. Over the past decade, many studies have investigated both miRNAs and lncRNAs in patients with MS. Since then, insightful knowledge has been gained in this field. Here, we review the role of miRNAs and lncRNAs in MS pathogenesis and discuss their implications for diagnosis and treatment.

Cortical and meningeal pathology in progressive multiple sclerosis: a new therapeutic target?

2019 ◽  
Vol 30 (3) ◽  
pp. 221-232 ◽  
Author(s):  
Berenice Anabel Silva ◽  
Carina Cintia Ferrari
Keyword(s):  
Multiple Sclerosis ◽  
Progressive Multiple Sclerosis ◽  
Cortical Lesions ◽  
Therapeutic Approaches ◽  
New Therapeutic Approaches ◽  
Meningeal Inflammation ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Therapeutic Alternatives ◽  
Ms Pathogenesis

Abstract Multiple sclerosis (MS) is an inflammatory and neurodegenerative disease that involves an intricate interaction between the central nervous system and the immune system. Nevertheless, its etiology is still unknown. MS exhibits different clinical courses: recurrent episodes with remission periods (‘relapsing-remitting’) that can evolve to a ‘secondary progressive’ form or persistent progression from the onset of the disease (‘primary progressive’). The discovery of an effective treatment and cure has been hampered due to the pathological and clinical heterogeneity of the disease. Historically, MS has been considered as a disease exclusively of white matter. However, patients with progressive forms of MS present with cortical lesions associated with meningeal inflammation along with physical and cognitive disabilities. The pathogenesis of the cortical lesions has not yet been fully described. Animal models that represent both the cortical and meningeal pathologies will be critical in addressing MS pathogenesis as well as the design of specific treatments. In this review, we will address the state-of-the-art diagnostic and therapeutic alternatives and the development of strategies to discover new therapeutic approaches, especially for the progressive forms.

Suppressor of cytokine signaling-1 in T cells and macrophages is critical for preventing lethal inflammation

Blood ◽  
2005 ◽  
Vol 106 (5) ◽  
pp. 1668-1675 ◽  
Author(s):  
Mark M. W. Chong ◽  
Donald Metcalf ◽  
Emma Jamieson ◽  
Warren S. Alexander ◽  
Thomas W. H. Kay
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inflammatory Disease ◽  
Lymphoid Cells ◽  
Interleukin 12 ◽  
Cytokine Signaling ◽  
Suppressor Of Cytokine Signaling ◽  
Cytokine Network ◽  
Activated T Cells ◽  
Ifn Γ

Abstract The balance between pro- and anti-inflammatory cytokines modulates inflammation. Intracellular inhibitors of signaling, in turn, contribute to the negative regulation of cytokines. One of these inhibitors is suppressor of cytokine signaling-1 (SOCS-1). Socs1-/- mice die by 3 weeks of age with inflammation and fatty necrosis of the liver. Here, cre/loxP deletion of Socs1 was used to investigate the contribution of specific cells/tissues to inflammatory disease. Mice with SOCS-1 deficiency in myeloid and lymphoid cells, but not lymphoid alone, became ill at 50 to 250 days of age. These mice developed splenomegaly and T-cell/macrophage infiltration of many organs, including liver, lung, pancreas, and muscle. There were also abnormally high levels of the proinflammatory cytokines interferon γ (IFN-γ), tumor necrosis factor (TNF), and interleukin-12 (IL-12), and activated T cells circulating in these mice. Socs1null T cells were found to be hypersensitive to multiple cytokines, including IL-1, IL-2, and IL-12, resulting in IFN-γ production without requiring T-cell receptor (TCR) ligation. Additionally, Socs1null macrophages produced excessive amounts of IL-12 and TNF in response to other cytokines, including IFN-γ. A dysregulated cytokine network between T cells and macrophages is thus associated with this inflammatory disease. These findings indicate that SOCS-1 is critical in both T cells and macrophages for preventing uncontrolled inflammation. (Blood. 2005;106:1668-1675)

scholarly journals Serum Anti-oligodendrocyte Autoantibodies in Patients With Multiple Sclerosis Detected by a Tissue-Based Immunofluorescence Assay

2021 ◽  
Vol 12 ◽  
Author(s):  
Yukino Miyachi ◽  
Takayuki Fujii ◽  
Ryo Yamasaki ◽  
Daisuke Tsuchimoto ◽  
Kyoko Iinuma ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Low Frequency ◽  
Immunofluorescence Assay ◽  
Mature Oligodendrocyte ◽  
Myelin Sheaths ◽  
Mental Disturbance ◽  
Disability Status ◽  
Relapsing Remitting ◽  
The Central Nervous System ◽  
Cns Proteins

Multiple sclerosis (MS), the most prevalent inflammatory disease of the central nervous system (CNS), is characterized by damaged to myelin sheaths and oligodendrocytes. Because MS patients have variable clinical courses and disease severities, it is important to identify biomarkers that predict disease activity and severity. In this study, we assessed the frequencies of serum autoantibodies against mature oligodendrocytes in MS patients using a tissue-based immunofluorescence assay (IFA) to determine whether anti-oligodendrocyte antibodies are associated with the clinical features of MS patients and whether they might be a biomarker to assess CNS tissue damage in MS patients. We assessed the binding of serum autoantibodies to mouse oligodendrocytes expressing Nogo-A, a reliable mature oligodendrocyte marker, by IFA with mouse brain and sera from 147 MS patients, comprising 103 relapsing–remitting MS (RRMS), 22 secondary progressive MS (SPMS), and 22 primary progressive MS (PPMS) patients, 38 neuromyelitis optica spectrum disorder (NMOSD) patients, 23 other inflammatory neurological disorder (OIND) patients, and 39 healthy controls (HCs). Western blotting (WB) was performed using extracted mouse cerebellum proteins and IgG from anti-oligodendrocyte antibody-positive MS patients. Tissue-based IFA showed that anti-oligodendrocyte antibodies were positive in 3/22 (13.6%) PPMS and 1/22 (4.5%) SPMS patients but not in RRMS, NMOSD, and OIND patients or HCs. WB demonstrated the target CNS proteins recognized by serum anti-oligodendrocyte antibodies were approximately 110 kDa and/or 150 kDa. Compared with anti-oligodendrocyte antibody-negative MS patients, MS patients with anti-oligodendrocyte antibodies were significantly older at the time of serum sampling, scored significantly higher on the Expanded Disability Status Scale and the Multiple Sclerosis Severity Score, and had a higher frequency of mental disturbance. Although the clinical significance of anti-oligodendrocyte antibodies is still unclear because of their low frequency, anti-oligodendrocyte autoantibodies are potential biomarkers for monitoring the disease pathology and progression in MS.

Sign in / Sign up

Export Citation Format

Share Document