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Multiple sclerosis, immunopathogenesis

Recai Türkoğlu, Murat Giriş, Mehmet Gencer, Uğur Akcan, Arda Örçen
INTRODUCTION: Prolactin has been discussed as a factor likely to play a mediating role in multiple sclerosis (MS). Our aim was to investigate the possible association between prolactin production and clinical features of autoimmune demyelinating central nervous system disorders. METHODS: Serum prolactin levels of 255 MS patients, 19 neuromyelitis optica (NMO) patients, 15 clinically isolated syndrome (CIS) patients, and 240 healthy controls were measured by a heterogeneous sandwich magnetic separation assay...
December 2016: Noro Psikiyatri Arsivi
Avadhesh Kumar Singh, Lenka Novakova, Markus Axelsson, Clas Malmeström, Henrik Zetterberg, Jan Lycke, Susanna L Cardell
We have identified a population of T lymphocytes in peripheral blood, Vδ1 TCRγδ T lymphocytes, which unexpectedly was uniquely expressing high production of interferon-γ in newly diagnosed, untreated multiple sclerosis (MS) patients. IFN-γ production in this population distinctly correlated to parameters of clinical disease activity, inflammation, and neuronal damage. These Vδ1 T lymphocytes belong to a population of innate T lymphocytes that recognize antigen in the context of CD1d/CD1c and which include reactivity to the myelin glycosphingolipid sulfatide...
2017: Frontiers in Immunology
Yifan Zhou, Ling Fang, Lisheng Peng, Wei Qiu
Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by axonal destruction and demyelination, which etiology and immunopathogenesis still remains uncertain. Although several lines of evidence show that myelin-reactive T cells play an essential role in the pathogenesis of MS, recent findings have pointed to the relevance of innate immune system such as Toll-like receptors (TLRs). TLRs have been assigned number 1 to 10 in human with different cellular location. Among them, TLR9 is one of the best studied nucleic acid sensing molecules...
February 15, 2017: Journal of the Neurological Sciences
Andrea Harrer, Georg Pilz, Katrin Oppermann, Marlene Sageder, Shahrzad Afazel, Elisabeth Haschke-Becher, Theo Rispens, Annick de Vries, Mark McCoy, Vlado Stevanovic, Wolfgang Hitzl, Eugen Trinka, Jörg Kraus, Johann Sellner, Peter Wipfler
Natalizumab (NZB) discontinuation during a treatment change is associated with recurrence of disease activity in a significant proportion of multiple sclerosis (MS) patients. The immunological basis why disease reactivation occurs in selected patients is unresolved. In search of a prognostic biomarker for a safe and effective transition from NZB to fingolimod, we monitored five parameters related to pharmacokinetic and pharmacodynamic effects of the two drugs in 12 MS patients until six months on fingolimod...
March 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
Fereshteh Alsahebfosoul, Ilnaz Rahimmanesh, Mansour Shajarian, Masoud Etemadifar, Nahid Sedaghat, Zahra Hejazi, Shamsi Naderi
Cytokines are implicated in the immunopathogenesis of multiple sclerosis (MS). Interleukin (IL)-33, one of the recently discovered members of the IL-1 superfamily, is a dual functional cytokine involved in various autoimmune disorders. In a case-control study, venous blood was collected from healthy subjects categorized as control group (n=44) and MS patients (n=44). All recruited patients were clinically diagnosed with relapsing-remitting MS (RRMS), including patients without treatment (new identified cases, n=16) and those treated with interferon beta (IFN-β) (n=28)...
March 1, 2017: Biomolecular Concepts
Xavier Montalban, Stephen L Hauser, Ludwig Kappos, Douglas L Arnold, Amit Bar-Or, Giancarlo Comi, Jérôme de Seze, Gavin Giovannoni, Hans-Peter Hartung, Bernhard Hemmer, Fred Lublin, Kottil W Rammohan, Krzysztof Selmaj, Anthony Traboulsee, Annette Sauter, Donna Masterman, Paulo Fontoura, Shibeshih Belachew, Hideki Garren, Nicole Mairon, Peter Chin, Jerry S Wolinsky
BACKGROUND: An evolving understanding of the immunopathogenesis of multiple sclerosis suggests that depleting B cells could be useful for treatment. We studied ocrelizumab, a humanized monoclonal antibody that selectively depletes CD20-expressing B cells, in the primary progressive form of the disease. METHODS: In this phase 3 trial, we randomly assigned 732 patients with primary progressive multiple sclerosis in a 2:1 ratio to receive intravenous ocrelizumab (600 mg) or placebo every 24 weeks for at least 120 weeks and until a prespecified number of confirmed disability progression events had occurred...
January 19, 2017: New England Journal of Medicine
Adrian Budhram, Seema Parvathy, Marcelo Kremenchutzky, Michael Silverman
BACKGROUND: The gut microbiome, which consists of a highly diverse ecologic community of micro-organisms, has increasingly been studied regarding its role in multiple sclerosis (MS) immunopathogenesis. This review critically examines the literature investigating the gut microbiome in MS. METHODS: A comprehensive search was performed of PubMed databases and ECTRIMS meeting abstracts for literature relating to the gut microbiome in MS. Controlled studies examining the gut microbiome in patients with MS were included for review...
December 1, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Jie Wu, Zhengquan Yu, Gang Chen
The central nervous system (CNS) was traditionally thought to tolerate inflammatory responses. However, CNS is not completely immune-privileged in recent researches. These responses including Microglia and macrophage activation and peripheral immune cells infiltration have been founded successively. Thus, the traditional view of the adult brain as an immune-privileged organ has been changed. Increasing evidence indicated that the PD-1(programmed cell death-1)/PD-Ls signal pathway plays an important role in regulating the immunopathogenesis of brain following injury...
November 23, 2016: Current Drug Delivery
J L Orthmann-Murphy, P A Calabresi
Multiple sclerosis (MS) is a heterogeneous inflammatory demyelinating disorder of the central nervous system (CNS). People with MS typically have a relapsing remitting disease course, with episodic neurological dysfunction corresponding to inflammation in the brain or spinal cord. Some relapsing patients develop a secondary progressive disease course, with accumulation of disability over time, yet other people with MS only experience a primary progressive course. Over the past 20 years, 14 immunomodulatory therapies have been approved in MS in order to reduce the frequency of inflammatory relapses and prevent CNS damage...
January 2017: Clinical Pharmacology and Therapeutics
Annukka Pietikäinen, Mikael Maksimow, Tommi Kauko, Saija Hurme, Marko Salmi, Jukka Hytönen
BACKGROUND: Lyme neuroborreliosis (LNB) is one of the manifestations of Lyme disease. Although it is known that immune reaction of LNB patients is dominated by Th1 and Th2 responses and patients have elevated numbers of B cells in their cerebrospinal fluid (CSF), not all the cells involved in inflammation and cytokine secretion have been characterized. The current diagnostics of LNB is based on intrathecal production of antibodies. In recent years, the measurement of chemokine CXCL13 concentration from the CSF has been introduced as a new promising diagnostic tool for LNB to complement the antibody-based diagnostic methods...
October 18, 2016: Journal of Neuroinflammation
Naeim Ehtesham, Fariborz Khorvash, Majid Kheirollahi
MicroRNAs (miRNAs) are crucial to the immunopathogenesis of multiple sclerosis (MS). The mechanism of action of interferon beta (IFN-β) in relapsing-remitting (RR) MS patients is largely unknown. miR-145 and miR-20a-5p previously reported as diagnosis biomarker in treatment naïve RRMS patients and their expression after IFN-β therapy might be indicative of molecular mechanism of IFN-β. Cross-talking between JAK/STAT pathway and complementary pathways like MAPK is important in IFN-β signaling. Here, in order to clarify the ambiguous molecular mechanism of IFN-β and evaluate the potential use of them as a biomarker for monitoring of therapy, we investigated the expression of miR-145 and miR-20a-5p in blood sample of 15 treatment naïve RRMS patients, 15 IFN-β-treated RRMS patients, and 15 healthy volunteers (HVs)...
January 2017: Journal of Molecular Neuroscience: MN
Jennifer N Hahn, Deepak K Kaushik, Manoj K Mishra, Jianxiong Wang, Claudia Silva, V Wee Yong
Extracellular matrix metalloproteinase inducer (EMMPRIN, CD147) is a transmembrane glycoprotein that is upregulated on leukocytes in active lesions in multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Administration of anti-EMMPRIN Abs reduces the severity of EAE. Minocycline is a tetracycline antibiotic with immune-modulatory properties that decreases the severity of EAE; it was recently found to attenuate the conversion from a first demyelinating event to clinically definite MS in a phase III trial...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Annie C Bowles, Amy L Strong, Rachel M Wise, Robert C Thomas, Brittany Y Gerstein, Maria F Dutreil, Ryan S Hunter, Jeffrey M Gimble, Bruce A Bunnell
Multiple sclerosis (MS) is a common neurodegenerative disease and remains an unmet clinical challenge. In MS, an autoimmune response leads to immune cell infiltration, inflammation, demyelination, and lesions in central nervous system (CNS) tissues resulting in tremors, fatigue, and progressive loss of motor function. These pathologic hallmarks are effectively reproduced in the murine experimental autoimmune encephalomyelitis (EAE) model. The stromal vascular fraction (SVF) of adipose tissue is composed of adipose-derived stromal/stem cells (ASC), adipocytes, and various leukocytes...
October 12, 2016: Stem Cells
Nazanin Arjomand Fard, Gholamreza Azizi, Abbas Mirshafiey
Multiple sclerosis is a complex disease with many different immune cells involved in its pathogenesis. Newly identified T helper cell 22 (Th22) is a subset of CD4(+) T cells with specific properties apart from other known CD4(+) T cell subsets with distinguished function and gene expression. Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-α (TNF- α). The frequency of Th22 and related cytokine IL-22 are increased in various autoimmune diseases...
July 2016: Innovations in Clinical Neuroscience
Valerio Chiurchiù, Alessandro Leuti, Maria Teresa Cencioni, Maria Albanese, Marco De Bardi, Tiziana Bisogno, Diego Centonze, Luca Battistini, Mauro Maccarrone
Monocytes are believed to be involved in the immunopathogenesis of multiple sclerosis (MS). The aim of this study was to investigate their role in MS and their immunomodulation by the endocannabinoid system (ECS), a novel target for the treatment of this disease. We compared the level of cytokine production from monocytes in healthy subjects and MS patients upon stimulation with viral or bacterial Toll-like receptors (TLR) and we evaluated the ECS immunomodulatory role in these cells. Here we show that MS monocytes produced more TNF-α, IL-12 and IL-6 following activation of TLR2/4 with LPS or of TLR5 with flagellin, as opposed to TLR7/8 stimulation with R848...
September 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
S Ljubisavljevic, I Stojanovic, J Basic, D A Pavlovic
Although current evidence mainly suggests immunopathogenesis of demyelination and neurodegeneration in multiple sclerosis (MS), there are results which document the importance of other factors, such as oxidative stress and its mediated injuries. The oxidative stress intensity in axonal damage during acute demyelination is little known. We performed this study as a cross-sectional biomarker validation study in order to evaluate the parameters of axonal damage (phosphorylated neurofilaments heavy chain (pNF-H)) and oxidative stress (8-hydroxy-2'-deoxyguanosine (8-OHdG)) in plasma of patients with initial and relapsing-remitting demyelination attacks, defined as clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RRMS); and the correlations between these parameters and biological (index of blood brain barrier (BBB) permeability), clinical (index of disease progression), and radiological (T1-Gd-enhancing lesion volume) activities of disease...
October 2016: Neurotoxicity Research
Vikram Bhise, Suhayl Dhib-Jalbut
INTRODUCTION: The understanding of the immunopathogenesis of multiple sclerosis (MS) has expanded with more research into T-cell subtypes, cytokine contributors, B-cell participation, mitochondrial dysfunction, and more. Treatment options have rapidly expanded with three relatively recent oral therapy alternatives entering the arena. AREAS COVERED: In the following review, we discuss current mechanisms of immune dysregulation in MS, how they relate to current treatments, and the impact these findings will have on the future of therapy...
October 2016: Expert Review of Clinical Immunology
Steffen Pfeuffer, Tobias Ruck, Christoph Kleinschnitz, Heinz Wiendl, Sven G Meuth
The treatment of multiple sclerosis (MS) remains challenging despite the great efforts made in the development of novel therapies. Driven by the growing knowledge of the immunopathogenesis of the disease, a plethora of new pharmacological agents have been developed and tested in clinical trials. However, the therapeutic advantages and positive clinical trials of some of these agents are outweighed by studies of promising agents that either failed due to negative or inconclusive results or had to be withdrawn because of serious unexpected adverse events...
June 2016: Expert Review of Neurotherapeutics
Todd A Hardy, W Oliver Tobin, Claudia F Lucchinetti
The availability of magnetic resonance imaging (MRI) has led to increasing recognition that multiple sclerosis (MS), tumefactive demyelination (TD) and Baló's concentric sclerosis (BCS) share many overlapping features. Baló-like lesions, which exhibit limited features of BCS, may represent an intermediate between BCS and typical MS demyelination. Lesions labeled as tumefactive are typically larger, but otherwise have much in common with conventional MS lesions, and TD and BCS lesions can also overlap. In this article, we explore the similarities between typical MS, TD and BCS cases, and reflect on the potential insights that intermediate or overlapping phenotypes may contribute towards an understanding of MS immunopathogenesis, and question whether these atypical forms of demyelination should be classified as separate demyelinating diseases, as different lesional manifestations of demyelination of any cause or as part of a spectrum with conventional MS...
July 2016: Multiple Sclerosis: Clinical and Laboratory Research
Nathalie Deckx, Barbara Willekens, Inez Wens, Bert O Eijnde, Herman Goossens, Pierre Van Damme, Zwi N Berneman, Nathalie Cools
Recent evidence suggests a key role of dendritic cells (DC) in the immunopathogenesis of multiple sclerosis (MS). Whereas dysfunction of DC was reported in MS patients, the underlying cause for this is not fully elucidated yet. The aim of the present study was to compare the gene expression profile of molecules involved in TLR4 and TLR7 signaling in DC from patients with MS and healthy controls. For this, circulating DC subsets were purified from patients with relapsing-remitting MS (RRMS) and from healthy controls for quantitative real-time PCR analysis...
May 2016: Innate Immunity
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