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Multiple sclerosis, immunopathogenesis

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https://www.readbyqxmd.com/read/27889994/pd-1-pd-ls-a-new-target-for-regulating-the-immunopathogenesis-in-central-nervous-system-disorders
#1
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
https://www.readbyqxmd.com/read/27804128/therapeutic-application-of-monoclonal-antibodies-in-multiple-sclerosis
#2
Jennifer L Orthmann-Murphy, Peter 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 progressive disease course, with accumulation of disability over time, yet other people with MS only experience a 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...
November 2, 2016: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/27756335/cerebrospinal-fluid-cytokines-in-lyme-neuroborreliosis
#3
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
https://www.readbyqxmd.com/read/27752929/mir-145-and-mir20a-5p-potentially-mediate-pleiotropic-effects-of-interferon-beta-through-mitogen-activated-protein-kinase-signaling-pathway-in-multiple-sclerosis-patients
#4
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)...
October 17, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27733550/impact-of-minocycline-on-extracellular-matrix-metalloproteinase-inducer-a-factor-implicated-in-multiple-sclerosis-immunopathogenesis
#5
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
https://www.readbyqxmd.com/read/27733015/adipose-stromal-vascular-fraction-mediated-improvements-at-late-stage-disease-in-a-murine-model-of-multiple-sclerosis
#6
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
https://www.readbyqxmd.com/read/27672486/the-potential-role-of-t-helper-cell-22-and-il-22-in-immunopathogenesis-of-multiple-sclerosis
#7
REVIEW
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
https://www.readbyqxmd.com/read/27616551/modulation-of-monocytes-by-bioactive-lipid-anandamide-in-multiple-sclerosis-involves-distinct-toll-like-receptors
#8
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
https://www.readbyqxmd.com/read/27295058/the-validation-study-of-neurofilament-heavy-chain-and-8-hydroxy-2-deoxyguanosine-as-plasma-biomarkers-of-clinical-paraclinical-activity-in-first-and-relapsing-remitting-demyelination-acute-attacks
#9
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
https://www.readbyqxmd.com/read/27191526/further-understanding-of-the-immunopathology-of-multiple-sclerosis-impact-on-future-treatments
#10
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
https://www.readbyqxmd.com/read/27058174/failed-interrupted-and-inconclusive-trials-on-relapsing-multiple-sclerosis-treatment-update-2010-2015
#11
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
https://www.readbyqxmd.com/read/27037180/exploring-the-overlap-between-multiple-sclerosis-tumefactive-demyelination-and-bal%C3%A3-s-concentric-sclerosis
#12
REVIEW
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
https://www.readbyqxmd.com/read/27036414/altered-molecular-expression-of-tlr-signaling-pathways-affects-the-steady-state-release-of-il-12p70-and-ifn-%C3%AE-in-patients-with-relapsing-remitting-multiple-sclerosis
#13
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
https://www.readbyqxmd.com/read/26996106/role-of-proangiogenic-factors-in-immunopathogenesis-of-multiple-sclerosis
#14
Kabir Magaji Hamid, Abbas Mirshafiey
Angiogenesis is a complex and balanced process in which new blood vessels form from preexisting ones by sprouting, splitting, growth and remodeling. This phenomenon plays a vital role in many physiological and pathological processes. However, the disturbance in physiological process can play a role in pathogenesis of some chronic inflammatory diseases, including multiple sclerosis (MS) in human and its animal model. Although the relation between abnormal blood vessels and MS lesions was established in previous studies, but the role of pathological angiogenesis remains unclear...
February 2016: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/26960979/the-role-of-adenosine-and-adenosine-receptors-in-the-immunopathogenesis-of-multiple-sclerosis
#15
REVIEW
Elham Safarzadeh, Farhad Jadidi-Niaragh, Morteza Motallebnezhad, Mehdi Yousefi
INTRODUCTION: Multiple sclerosis (MS) is a heterogeneous neurological disorder with multifactorial etiologies characterized by demyelination, axonal degeneration, and oligodendroglial death. It is believed that both genetics and environmental risk factors such as infection are involved in disease etiology. Accumulating evidence indicates that alteration in purinergic system signaling is involved in immunity and inflammation. Adenosine, a key purine nucleoside, has been shown to be produced during metabolic stress, including ischemia, inflammatory condition, and tissue injury...
July 2016: Inflammation Research: Official Journal of the European Histamine Research Society ... [et Al.]
https://www.readbyqxmd.com/read/26950113/the-immunology-of-neuromyelitis-optica-current-knowledge-clinical-implications-controversies-and-future-perspectives
#16
REVIEW
Michalina Jasiak-Zatonska, Alicja Kalinowska-Lyszczarz, Slawomir Michalak, Wojciech Kozubski
Neuromyelitis optica (NMO) is an autoimmune, demyelinating disorder of the central nervous system (CNS) with typical clinical manifestations of optic neuritis and acute transverse myelitis attacks. Previously believed to be a variant of multiple sclerosis (MS), it is now considered an independent disorder which needs to be differentiated from MS. The discovery of autoantibodies against aquaporin-4 (AQP4-IgGs) changed our understanding of NMO immunopathogenesis and revolutionized the diagnostic process. AQP4-IgG is currently regarded as a specific biomarker of NMO and NMO spectrum disorders (NMOsd) and a key factor in its pathogenesis...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/26919719/b-cell-th17-and-neutrophil-related-cerebrospinal-fluid-cytokine-chemokines-are-elevated-in-mog-antibody-associated-demyelination
#17
Kavitha Kothur, Louise Wienholt, Esther M Tantsis, John Earl, Sushil Bandodkar, Kristina Prelog, Fiona Tea, Sudarshini Ramanathan, Fabienne Brilot, Russell C Dale
BACKGROUND: Myelin oligodendrocyte glycoprotein antibody (MOG Ab) associated demyelination represents a subgroup of autoimmune demyelination that is separate from multiple sclerosis and aquaporin 4 IgG-positive NMO, and can have a relapsing course. Unlike NMO and MS, there is a paucity of literature on immunopathology and CSF cytokine/chemokines in MOG Ab associated demyelination. AIM: To study the differences in immunopathogenesis based on cytokine/chemokine profile in MOG Ab-positive (POS) and -negative (NEG) groups...
2016: PloS One
https://www.readbyqxmd.com/read/26903712/12-weeks-of-combined-endurance-and-resistance-training-reduces-innate-markers-of-inflammation-in-a-randomized-controlled-clinical-trial-in-patients-with-multiple-sclerosis
#18
Nathalie Deckx, Inez Wens, Amber H Nuyts, Niel Hens, Benedicte Y De Winter, Gudrun Koppen, Herman Goossens, Pierre Van Damme, Zwi N Berneman, Bert O Eijnde, Nathalie Cools
Previously, we reported that patients with multiple sclerosis (MS) demonstrate improved muscle strength, exercise tolerance, and lean tissue mass following a combined endurance and resistance exercise program. However, the effect of exercise on the underlying disease pathogenesis remains elusive. Since recent evidence supports a crucial role of dendritic cells (DC) in the pathogenesis of MS, we investigated the effect of a 12-week combined exercise program in MS patients on the number and function of DC. We demonstrate an increased number of plasmacytoid DC (pDC) following the exercise program...
2016: Mediators of Inflammation
https://www.readbyqxmd.com/read/26857496/il-12r%C3%AE-2-has-a-protective-role-in-relapsing-remitting-experimental-autoimmune-encephalomyelitis
#19
Chong Xie, Bogoljub Ciric, Shuo Yu, Guang-Xian Zhang, Abdolmohamad Rostami
IL-12Rβ2 is a common receptor subunit of heterodimeric receptors for IL-12 and IL-35, two cytokines that are implicated in immunopathogenesis of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. We evaluated the role of IL-12Rβ2 in relapsing-remitting EAE (RR-EAE). IL-12Rβ2-deficient SJL/J mice developed markedly more severe clinical EAE, and had greater mortality and more severe relapses compared with wild-type controls. IL-12Rβ2-deficient EAE mice also had more infiltrating mononuclear cells in the CNS, as well as higher T cell proliferative capacity and decreased IFN-γ production at the periphery...
February 15, 2016: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/26773145/cutting-edge-cd99-is-a-novel-therapeutic-target-for-control-of-t-cell-mediated-central-nervous-system-autoimmune-disease
#20
Ryan C Winger, Christopher T Harp, Ming-Yi Chiang, David P Sullivan, Richard L Watson, Evan W Weber, Joseph R Podojil, Stephen D Miller, William A Muller
Leukocyte trafficking into the CNS is a prominent feature driving the immunopathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. Blocking the recruitment of inflammatory leukocytes into the CNS represents an exploitable therapeutic target; however, the adhesion molecules that specifically regulate the step of leukocyte diapedesis into the CNS remain poorly understood. We report that CD99 is critical for lymphocyte transmigration without affecting adhesion in a human blood-brain barrier model...
February 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
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