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Myelin oligodendrocyte antibodies

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https://www.readbyqxmd.com/read/28340598/myelin-specific-multiple-sclerosis-antibodies-cause-complement-dependent-oligodendrocyte-loss-and-demyelination
#1
Yiting Liu, Katherine S Given, Danielle E Harlow, Adeline M Matschulat, Wendy B Macklin, Jeffrey L Bennett, Gregory P Owens
Intrathecal immunoglobulin G (IgG) synthesis, cerebrospinal fluid (CSF) oligoclonal IgG bands and lesional IgG deposition are seminal features of multiple sclerosis (MS) disease pathology. Both the specific targets and pathogenic effects of MS antibodies remain poorly characterized. We produced IgG1 monoclonal recombinant antibodies (rAbs) from clonally-expanded plasmablasts recovered from MS patient CSF. Among these were a subset of myelin-specific MS rAbs. We examined their immunoreactivity to mouse organotypic cerebellar slices by live binding and evaluated tissue injury in the presence and absence of human complement...
March 24, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/28327523/methodological-challenges-in-protein-microarray-and-immunohistochemistry-for-the-discovery-of-novel-autoantibodies-in-paediatric-acute-disseminated-encephalomyelitis
#2
Patrick Peschl, Melanie Ramberger, Romana Höftberger, Karin Jöhrer, Matthias Baumann, Kevin Rostásy, Markus Reindl
Acute disseminated encephalomyelitis (ADEM) is a rare autoimmune-mediated demyelinating disease affecting mainly children and young adults. Differentiation to multiple sclerosis is not always possible, due to overlapping clinical symptoms and recurrent and multiphasic forms. Until now, immunoglobulins reactive to myelin oligodendrocyte glycoprotein (MOG antibodies) have been found in a subset of patients with ADEM. However, there are still patients lacking autoantibodies, necessitating the identification of new autoantibodies as biomarkers in those patients...
March 22, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28326889/aquaporin-4-autoimmunity-in-patients-with-systemic-lupus-erythematosus-a-predominantly-population-based-study
#3
Nasrin Asgari, Sven Jarius, Helle Laustrup, Hanne Pb Skejoe, Soeren T Lillevang, Brian G Weinshenker, Anne Voss
BACKGROUND: Serum immunoglobulin G targeting the astrocyte water channel aquaporin-4 (AQP4) in the central nervous system (CNS) is a biomarker for neuromyelitis optica spectrum disease (NMOSD). Co-existence of NMOSD with systemic lupus erythematosus (SLE) putatively suggests susceptibility to antibody-mediated autoimmune disease. OBJECTIVE: To estimate the prevalence of NMOSD in SLE and investigate the immunogenetic background for an association of NMOSD and SLE...
March 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28326060/microbial-neuraminidase-induces-a-moderate-and-transient-myelin-vacuolation-independent-of-complement-system-activation
#4
Pablo Granados-Durán, María Dolores López-Ávalos, Manuel Cifuentes, Margarita Pérez-Martín, María Del Mar Fernández-Arjona, Timothy R Hughes, Krista Johnson, B Paul Morgan, Pedro Fernández-Llebrez, Jesús M Grondona
AIMS: Some central nervous system pathogens express neuraminidase (NA) on their surfaces. In the rat brain, a single intracerebroventricular (ICV) injection of NA induces myelin vacuolation in axonal tracts. Here, we explore the nature, the time course, and the role of the complement system in this damage. METHODS: The spatiotemporal analysis of myelin vacuolation was performed by optical and electron microscopy. Myelin basic protein-positive area and oligodendrocyte transcription factor (Olig2)-positive cells were quantified in the damaged bundles...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28306572/neuromyelitis-optica-and-neuromyelitis-optica-spectrum-disorders
#5
Romain Marignier, Alvaro Cobo Calvo, Sandra Vukusic
PURPOSE OF REVIEW: The discovery of highly specific auto-antibodies directed against the water channel aquaporin 4 was a quantum leap in the definition, classification and management of neuromyelitis optica (NMO). Herein, we propose an update on epidemiological, clinical and therapeutic advances in the field, underlining unmet needs. RECENT FINDINGS: Large-scale epidemiological studies have recently provided a more precise evaluation of NMO prevalence and a better stratification regarding ethnicity and sex...
March 16, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28302134/microrna-142-regulates-inflammation-and-t-cell-differentiation-in-an-animal-model-of-multiple-sclerosis
#6
Farideh Talebi, Samira Ghorbani, Wing Fuk Chan, Roobina Boghozian, Farimah Masoumi, Sedigheh Ghasemi, Mohammed Vojgani, Christopher Power, Farshid Noorbakhsh
BACKGROUND: MicroRNAs have emerged as an important class of modulators of gene expression. These molecules influence protein synthesis through translational repression or degradation of mRNA transcripts. Herein, we investigated the potential role of miR-142a isoforms, miR-142a-3p and miR-142a-5p, in the context of autoimmune neuroinflammation. METHODS: The expression levels of two mature isoforms of miR-142 were measured in the brains of patients with multiple sclerosis (MS) and the CNS tissues from mice with experimental autoimmune encephalomyelitis (EAE), an animal model of MS...
March 16, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28248700/myelin-oligodendrocyte-glycoprotein-antibodies-how-clinically-useful-are-they
#7
Markus Reindl, Sven Jarius, Kevin Rostasy, Thomas Berger
PURPOSE OF REVIEW: Serum IgG autoantibodies against the myelin oligodendrocyte glycoprotein (MOG) are present in atypical demyelinating disorders such as neuromyelitis optica spectrum disorders (NMOSD) or acute disseminated encephalomyelitis. Whereas the role of aquaporin-4 antibodies as diagnostic markers for NMOSD is meanwhile well established, the role of MOG antibodies is less clear. RECENT FINDINGS: Initial studies suggested that MOG antibodies are associated with a more benign disease course than aquaporin-4antibodies...
February 28, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28193690/lingo-1-regulates-oligodendrocyte-differentiation-through-the-cytoplasmic-gelsolin-signaling-pathway
#8
Zhaohui Shao, Xinhua Lee, Guanrong Huang, Guoqing Sheng, Christopher E Henderson, Daniel Louvard, Jiho Sohn, Blake Pepinsky, Sha Mi
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. How actin dynamics is regulated during this process remains poorly understood. Leucine rich repeat and Immunoglobulin-like domain-containing Nogo receptor interacting protein 1(LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28170189/mesenchymal-stem-cells-yield-transient-improvements-in-motor-function-in-an-infant-rhesus-macaque-with-severe-early-onset-krabbe-disease
#9
Irina A Isakova, Kate C Baker, Jason Dufour, Donald G Phinney
Krabbe disease, or globoid cell leukodystrophy, is a rare disorder caused by deficient galactosylceramidase activity and loss of myelin-forming oligodendrocytes, resulting in progressive demyelination and severely impaired motor function. Disease symptoms in humans appear within 3-6 months of age (early infantile) and manifest as marked irritability, spasticity, and seizures. The disease is often fatal by the second year of life, with few effective treatment options. Herein we evaluated the therapeutic potential of mesenchymal stem cells (MSCs) administered intracranially to a 1-month-old rhesus macaque diagnosed with severe early-onset Krabbe disease that displayed neurologic and behavioral symptoms similar to those of human patients...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28125740/retinal-nerve-fiber-layer-may-be-better-preserved-in-mog-igg-versus-aqp4-igg-optic-neuritis-a-cohort-study
#10
Hadas Stiebel-Kalish, Itay Lotan, Judith Brody, Gabriel Chodick, Omer Bialer, Romain Marignier, Michael Bach, Mark Andrew Hellmann
BACKGROUND: Optic neuritis (ON) in patients with anti-myelin oligodendrocyte glycoprotein (MOG)-IgG antibodies has been associated with a better clinical outcome than anti-aquaporin 4 (AQP4)- IgG ON. Average retinal nerve fiber layer thickness (RNFL) correlates with visual outcome after ON. OBJECTIVES: The aim of this study was to examine whether anti-MOG-IgG ON is associated with better average RNFL compared to anti-AQP4-IgG ON, and whether this corresponds with a better visual outcome...
2017: PloS One
https://www.readbyqxmd.com/read/28111033/azathioprine-therapy-in-a-case-of-pediatric-multiple-sclerosis-that-was-seropositive-for-mog-igg
#11
Yifan Zhou, Qiao Huang, Tingting Lu, Xiaobo Sun, Ling Fang, Zhengqi Lu, Xueqiang Hu, Allan Kermode, Wei Qiu
There is a lack of evidence for treatment of pediatric multiple sclerosis (PedMS). Treatment using azathioprine for PedMS has not been reported. A 10-year-old boy with multiple sclerosis who was seropositive for antibodies against myelin oligodendrocyte glycoprotein (MOG)-IgG was treated with azathioprine plus oral methylprednisolone. The patient showed clinical and magnetic resonance imaging stability, with MOG-IgG seroconversion. There were no major side effects over a 5-year period. Azathioprine may be a treatment option, particularly in poor medical resource areas, for pediatric patients with multiple sclerosis who are seropositive for MOG-IgG...
April 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28105459/mog-antibody-positive-benign-unilateral-cerebral-cortical-encephalitis-with-epilepsy
#12
Ryo Ogawa, Ichiro Nakashima, Toshiyuki Takahashi, Kimihiko Kaneko, Tetsuya Akaishi, Yoshiki Takai, Douglas Kazutoshi Sato, Shuhei Nishiyama, Tatsuro Misu, Hiroshi Kuroda, Masashi Aoki, Kazuo Fujihara
OBJECTIVE: To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody. METHODS: In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody-positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008-2014)...
March 2017: Neurology® Neuroimmunology & Neuroinflammation
https://www.readbyqxmd.com/read/28057865/cocapture-of-cognate-and-bystander-antigens-can-activate-autoreactive-b-cells
#13
Nicholas S R Sanderson, Maria Zimmermann, Luca Eilinger, Céline Gubser, Nicole Schaeren-Wiemers, Raija L P Lindberg, Stephanie K Dougan, Hidde L Ploegh, Ludwig Kappos, Tobias Derfuss
Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) are associated with autoimmune central nervous system diseases like acute disseminated encephalomyelitis (ADEM). For ADEM, it is speculated that a preceding infection is the trigger of the autoimmune response, but the mechanism connecting the infection to the production of MOG antibodies remains a mystery. We reasoned that the ability of B cells to capture cognate antigen from cell membranes, along with small quantities of coexpressed "bystander" antigens, might enable B-cell escape from tolerance...
January 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28057080/combination-of-alpha-synuclein-immunotherapy-with-anti-inflammatory-treatment-in-a-transgenic-mouse-model-of-multiple-system-atrophy
#14
Elvira Valera, Brian Spencer, Jerel A Fields, Ivy Trinh, Anthony Adame, Michael Mante, Edward Rockenstein, Paula Desplats, Eliezer Masliah
Multiple system atrophy (MSA) is a fatal neurodegenerative disorder characterized by the pathological accumulation of alpha-synuclein (α-syn) in oligodendrocytes. Therapeutic efforts to stop or delay the progression of MSA have yielded suboptimal results in clinical trials, and there are no efficient treatments currently available for MSA patients. We hypothesize that combining therapies targeting different aspects of the disease may lead to better clinical outcomes. To test this hypothesis, we combined the use of a single-chain antibody targeting α-syn modified for improved central nervous system penetration (CD5-D5) with an unconventional anti-inflammatory treatment (lenalidomide) in the myelin basic protein (MBP)-α-syn transgenic mouse model of MSA...
January 5, 2017: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27988845/an-updated-histological-classification-system-for-multiple-sclerosis-lesions
#15
Tanja Kuhlmann, Samuel Ludwin, Alexandre Prat, Jack Antel, Wolfgang Brück, Hans Lassmann
Multiple sclerosis is a complex and heterogeneous, most likely autoimmune, demyelinating disease of the central nervous system (CNS). Although a number of histological classification systems for CNS lesions have been used by different groups in recent years, no uniform classification exists. In this paper, we propose a simple and unifying classification of MS lesions incorporating many elements of earlier histological systems that aims to provide guidelines for neuropathologists and researchers studying MS lesions to allow for better comparison of different studies performed with MS tissue, and to aid in understanding the pathogenesis of the disease...
January 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/27976382/early-glycolipid-poa-in-pro-oligodendroblasts-revealed-to-be-sulfatide-an-editorial-highlight-for-sulfatide-species-with-various-fatty-acid-chains-in-oligodendrocytes-at-different-developmental-stages-determined-by-imaging-mass-spectrometry
#16
EDITORIAL
Joan M Boggs
This Editorial highlights a study by Hirahara et al. J. Neurochem. (2016) in the current issue of the Journal of Neurochemistry, in which the authors used mass spectrometry to detect sulfatide with short chain fatty acids, C16, C18, and C18:0H in pro-oligodendroblasts at embryonic stages. These findings show that sulfatide is the pro-oligodendroblast antigen(POA) glycolipid that reacts with O4 monoclonal antibody. The different sulfatide species may perform different roles during cell development and in myelin...
December 15, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27951522/brain-lesion-distribution-criteria-distinguish-ms-from-aqp4-antibody-nmosd-and-mog-antibody-disease
#17
Maciej Juryńczyk, George Tackley, Yazhuo Kong, Ruth Geraldes, Lucy Matthews, Mark Woodhall, Patrick Waters, Wilhelm Kuker, Matthew Craner, Andrew Weir, Gabriele C DeLuca, Stephane Kremer, Maria Isabel Leite, Angela Vincent, Anu Jacob, Jérôme de Sèze, Jacqueline Palace
IMPORTANCE: Neuromyelitis optica spectrum disorders (NMOSD) can present with very similar clinical features to multiple sclerosis (MS), but the international diagnostic imaging criteria for MS are not necessarily helpful in distinguishing these two diseases. OBJECTIVE: This multicentre study tested previously reported criteria of '(1) at least 1 lesion adjacent to the body of the lateral ventricle and in the inferior temporal lobe; or (2) the presence of a subcortical U-fibre lesion or (3) a Dawson's finger-type lesion' in an independent cohort of relapsing-remitting multiple sclerosis (RRMS) and AQP4-ab NMOSD patients and also assessed their value in myelin oligodendrocyte glycoprotein (MOG)-ab positive and ab-negative NMOSD...
February 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/27906756/optic-neuritis-the-eye-as-a-window-to-the-brain
#18
Thomas M Jenkins, Ahmed T Toosy
PURPOSE OF REVIEW: Acute optic neuritis is a common clinical problem, requiring a structured assessment to guide management and prevent visual loss. The optic nerve is the most accessible part of the central nervous system, so optic neuritis also represents an important paradigm to help decipher mechanisms of damage and recovery in the central nervous system. Important developments include the advent of optical coherence tomography as a biomarker of central nervous system axonal loss, the discovery of new pathological antibodies, notably against aquaporin-4 and, more recently, myelin oligodendrocyte protein, and emerging evidence for sodium channel blockade as a novel therapeutic approach to address energy failure in neuroinflammatory disease...
February 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/27861899/sulfatide-species-with-various-fatty-acid-chains-in-oligodendrocytes-at-different-developmental-stages-determined-by-imaging-mass-spectrometry
#19
Yukie Hirahara, Taketoshi Wakabayashi, Tetsuji Mori, Taro Koike, Ikuko Yao, Masayuki Tsuda, Koichi Honke, Hitoshi Gotoh, Katsuhiko Ono, Hisao Yamada
HSO3-3-galactosylceramide (Sulfatide) species comprise the major glycosphingolipid components of oligodendrocytes and myelin and play functional roles in the regulation of oligodendrocyte maturation and myelin formation. Although various sulfatide species contain different fatty acids, it is unclear how these sulfatide species affect oligodendrogenesis and myelination. The O4 monoclonal antibody reaction with sulfatide has been widely used as a useful marker for oligodendrocytes and myelin. However, sulfatide synthesis during the pro-oligodendroblast stage, where differentiation into the oligodendrocyte lineage has already occurred, has not been examined...
November 12, 2016: Journal of Neurochemistry
https://www.readbyqxmd.com/read/27848954/myelinosome-formation-represents-an-early-stage-of-oligodendrocyte-damage-in-multiple-sclerosis-and-its-animal-model
#20
Elisa Romanelli, Doron Merkler, Aleksandra Mezydlo, Marie-Theres Weil, Martin S Weber, Ivana Nikić, Stephanie Potz, Edgar Meinl, Florian E H Matznick, Mario Kreutzfeldt, Alexander Ghanem, Karl-Klaus Conzelmann, Imke Metz, Wolfgang Brück, Matthew Routh, Mikael Simons, Derron Bishop, Thomas Misgeld, Martin Kerschensteiner
Oligodendrocyte damage is a central event in the pathogenesis of the common neuroinflammatory condition, multiple sclerosis (MS). Where and how oligodendrocyte damage is initiated in MS is not completely understood. Here, we use a combination of light and electron microscopy techniques to provide a dynamic and highly resolved view of oligodendrocyte damage in neuroinflammatory lesions. We show that both in MS and in its animal model structural damage is initiated at the myelin sheaths and only later spreads to the oligodendrocyte cell body...
November 16, 2016: Nature Communications
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