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EBV and multiple sclerosis

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https://www.readbyqxmd.com/read/28855411/epstein-barr-virus-cytomegalovirus-and-multiple-sclerosis-susceptibility-a-multiethnic-study
#1
Annette Langer-Gould, Jun Wu, Robyn Lucas, Jessica Smith, Edlin Gonzales, Lilyana Amezcua, Samantha Haraszti, Lie Hong Chen, Hong Quach, Judith A James, Lisa F Barcellos, Anny H Xiang
OBJECTIVE: To determine whether Epstein-Barr virus (EBV) or cytomegalovirus (CMV) seropositivity is associated with multiple sclerosis (MS) in blacks and Hispanics and to what extent measures of the hygiene hypothesis or breastfeeding could explain these findings. EBV and CMV have been associated with MS risk in whites, and the timing and frequency of both viruses vary by factors implicated in the hygiene hypothesis. METHODS: Incident cases of MS or its precursor, clinically isolated syndrome (CIS), and matched controls (blacks, 111 cases/128 controls; Hispanics, 173/187; whites, 235/256) were recruited from the membership of Kaiser Permanente Southern California...
August 30, 2017: Neurology
https://www.readbyqxmd.com/read/28767147/programmed-death-1-is-highly-expressed-on-cd8-cd57-t-cells-in-patients-with-stable-multiple-sclerosis-and-inhibits-their-cytotoxic-response-to-ebv
#2
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the CNS of patients with Multiple Sclerosis (pwMS) as a possible cause of disease. In this study, we have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 pwMS in active and inactive disease. We have measured the expression of markers of degranulation, the release of cytokines, cytotoxicity and the regulation of effector functions by inhibitory receptors, such as programmed death-1 (PD-1) and human inhibitor receptor Ig-like transcript 2 (ILT2)...
August 2, 2017: Immunology
https://www.readbyqxmd.com/read/28755684/epstein-barr-virus-and-multiple-sclerosis-updating-pender-s-hypothesis
#3
REVIEW
Martin Laurence, Julián Benito-León
Substantial epidemiological evidence supports the involvement of the Epstein-Barr virus (EBV) in multiple sclerosis (MS). Mechanisms through which EBV may increase MS risk are reviewed here. Most individuals contract EBV in early childhood yet only develop MS in early adulthood, by which time EBV has been latent for decades. When latent, EBV is confined to a minute subset of memory B cells: about 1000 cells in peripheral blood and 500,000 cells in the lymphoid system, mainly in the mouth. Reactivation of EBV in the central nervous system (CNS) has been proposed as a cause of MS...
August 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28755681/ebv-and-ms-major-cause-minor-contribution-or-red-herring
#4
REVIEW
Sean Burnard, Jeannette Lechner-Scott, Rodney J Scott
Multiple Sclerosis (MS) is a chronic neurological disease with genetic and environmental risk factors. Epstein Barr-Virus (EBV) has been closely associated with MS but with a significant amount of conflicting evidence. Some of the evidence for EBV involvement in MS includes: almost 100% of MS patients showing past EBV infection, an association with Infectious Mononucleosis (acute EBV infection), higher titres of EBV antibodies associated with an increased risk of MS development, and an overall altered immune response to EBV found in peripheral blood and the CNS of MS patients...
August 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28731372/exploring-the-effect-of-vitamin-d3-supplementation-on-the-anti-ebv-antibody-response-in-relapsing-remitting-multiple-sclerosis
#5
Linda Rolf, Anne-Hilde Muris, Amandine Mathias, Renaud Du Pasquier, Inga Koneczny, Giulio Disanto, Jens Kuhle, Sreeram Ramagopalan, Jan Damoiseaux, Joost Smolders, Raymond Hupperts
BACKGROUND: Epstein-Barr virus (EBV) infection and vitamin D insufficiency are potentially interacting risk factors for multiple sclerosis (MS). OBJECTIVES: To investigate the effect of high-dose vitamin D3 supplements on antibody levels against the EBV nuclear antigen-1 (EBNA-1) in patients with relapsing-remitting multiple sclerosis (RRMS) and to explore any underlying mechanism affecting anti-EBNA-1 antibody levels. METHODS: This study utilized blood samples from a randomized controlled trial in RRMS patients receiving either vitamin D3 (14,000 IU/day; n = 30) or placebo ( n = 23) over 48 weeks...
July 1, 2017: Multiple Sclerosis: Clinical and Laboratory Research
https://www.readbyqxmd.com/read/28729867/exposure-to-the-epstein-barr-viral-antigen-latent-membrane-protein-1-induces-myelin-reactive-antibodies-in-vivo
#6
Yakov Lomakin, Georgii Pavlovich Arapidi, Alexander Chernov, Rustam Ziganshin, Evgenii Tcyganov, Irina Lyadova, Ivan Olegovich Butenko, Maria Osetrova, Natalia Ponomarenko, Georgy Telegin, Vadim Markovich Govorun, Alexander Gabibov, Alexey Belogurov
Multiple sclerosis (MS) is an autoimmune chronic inflammatory disease of the central nervous system (CNS). Cross-reactivity of neuronal proteins with exogenous antigens is considered one of the possible mechanisms of MS triggering. Previously, we showed that monoclonal myelin basic protein (MBP)-specific antibodies from MS patients cross-react with Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1). In this study, we report that exposure of mice to LMP1 results in induction of myelin-reactive autoantibodies in vivo...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28654678/genetic-factors-affecting-ebv-copy-number-in-lymphoblastoid-cell-lines-derived-from-the-1000-genome-project-samples
#7
Rajendra Mandage, Marco Telford, Juan Antonio Rodríguez, Xavier Farré, Hafid Layouni, Urko M Marigorta, Caitlin Cundiff, Jose Maria Heredia-Genestar, Arcadi Navarro, Gabriel Santpere
Epstein-Barr virus (EBV), human herpes virus 4, has been classically associated with infectious mononucleosis, multiple sclerosis and several types of cancers. Many of these diseases show marked geographical differences in prevalence, which points to underlying genetic and/or environmental factors. Those factors may include a different susceptibility to EBV infection and viral copy number among human populations. Since EBV is commonly used to transform B-cells into lymphoblastoid cell lines (LCLs) we hypothesize that differences in EBV copy number among individual LCLs may reflect differential susceptibility to EBV infection...
2017: PloS One
https://www.readbyqxmd.com/read/28624961/phenotypic-and-functional-characterization-of-t-cells-in-white-matter-lesions-of-multiple-sclerosis-patients
#8
Gijsbert P van Nierop, Marvin M van Luijn, Samira S Michels, Marie-Jose Melief, Malou Janssen, Anton W Langerak, Werner J D Ouwendijk, Rogier Q Hintzen, Georges M G M Verjans
T cells are considered pivotal in the pathology of multiple sclerosis (MS), but their function and antigen specificity are unknown. To unravel the role of T cells in MS pathology, we performed a comprehensive analysis on T cells recovered from paired blood, cerebrospinal fluid (CSF), normal-appearing white matter (NAWM) and white matter lesions (WML) from 27 MS patients with advanced disease shortly after death. The differentiation status of T cells in these compartments was determined by ex vivo flow cytometry and immunohistochemistry...
June 17, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28624334/seasonality-and-autoimmune-diseases-the-contribution-of-the-four-seasons-to-the-mosaic-of-autoimmunity
#9
REVIEW
Abdulla Watad, Shir Azrielant, Nicola Luigi Bragazzi, Kassem Sharif, Paula David, Itay Katz, Gali Aljadeff, Mariana Quaresma, Galya Tanay, Mohammad Adawi, Howard Amital, Yehuda Shoenfeld
Autoimmune diseases (ADs) are a heterogeneous groups of diseases that occur as a results of loss of tolerance to self antigens. While the etiopathogeneis remain obscure, different environmental factors were suggested to have a role in the development of autoimmunity, including infections, low vitamin D levels, UV radiation, and melatonin. Interestingly, such factors possess seasonal variation patterns that could influence disease development, severity and progression. Vitamin D levels which reach a nadir during late winter and early spring is correlated with increased disease activity, clinical severity as well as relapse rates in several disease entities including multiple sclerosis (MS), non-cutaneous flares of systemic lupus erythematosus (SLE), psoriasis, and rheumatoid arthritis (RA)...
August 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28620346/primary-progressive-multiple-sclerosis-putting-together-the-puzzle
#10
REVIEW
Ahmed Abdelhak, Martin S Weber, Hayrettin Tumani
The focus of multiple sclerosis research has recently turned to the relatively rare and clearly more challenging condition of primary progressive multiple sclerosis (PPMS). Many risk factors such as genetic susceptibility, age, and Epstein-Barr virus (EBV) infection may interdepend on various levels, causing a complex pathophysiological cascade. Variable pathological mechanisms drive disease progression, including inflammation-associated axonal loss, continuous activation of central nervous system resident cells, such as astrocytes and microglia as well as mitochondrial dysfunction and iron accumulation...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28607749/an-essential-role-of-virus-infected-b-cells-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#11
REVIEW
Bert A 't Hart, Yolanda S Kap
Infection with Epstein-Barr virus (EBV) has been associated with an enhanced risk of genetically susceptible individuals to develop multiple sclerosis (MS). However, an explanation for the contrast between the high EBV infection prevalence (60-90%) and the low MS prevalence (0.1%) eludes us. Here we propose a new concept for the EBV-MS association developed in the experimental autoimmune encephalomyelitis model in marmoset monkeys, which are naturally infected with the EBV-related γ1-herpesvirus CalHV3. The data indicate that the infection of B cells with a γ1-herpesvirus endows them with the capacity to activate auto-aggressive CD8+ T cells specific for myelin oligodendrocyte glycoprotein...
January 2017: Multiple Sclerosis Journal—Experimental, Translational and Clinical
https://www.readbyqxmd.com/read/28604802/serological-profiling-of-the-ebv-immune-response-in-chronic-fatigue-syndrome-using-a-peptide-microarray
#12
Madlen Loebel, Maren Eckey, Franziska Sotzny, Elisabeth Hahn, Sandra Bauer, Patricia Grabowski, Johannes Zerweck, Pavlo Holenya, Leif G Hanitsch, Kirsten Wittke, Peter Borchmann, Jens-Ulrich Rüffer, Falk Hiepe, Klemens Ruprecht, Uta Behrends, Carola Meindl, Hans-Dieter Volk, Ulf Reimer, Carmen Scheibenbogen
BACKGROUND: Epstein-Barr-Virus (EBV) plays an important role as trigger or cofactor for various autoimmune diseases. In a subset of patients with Chronic Fatigue Syndrome (CFS) disease starts with infectious mononucleosis as late primary EBV-infection, whereby altered levels of EBV-specific antibodies can be observed in another subset of patients. METHODS: We performed a comprehensive mapping of the IgG response against EBV comparing 50 healthy controls with 92 CFS patients using a microarray platform...
2017: PloS One
https://www.readbyqxmd.com/read/28592428/ebv-infection-empowers-human-b-cells-for-autoimmunity-role-of-autophagy-and-relevance-to-multiple-sclerosis
#13
Elena Morandi, S Anwar Jagessar, Bert A 't Hart, Bruno Gran
The efficacy of B cell depletion therapy in multiple sclerosis indicates their central pathogenic role in disease pathogenesis. The B lymphotropic EBV is a major risk factor in multiple sclerosis, via as yet unclear mechanisms. We reported in a nonhuman primate experimental autoimmune encephalomyelitis model that an EBV-related lymphocryptovirus enables B cells to protect a proteolysis-sensitive immunodominant myelin oligodendrocyte glycoprotein (MOG) epitope (residues 40-48) against destructive processing...
July 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28574826/leflunomide-teriflunomide-inhibit-epstein-barr-virus-ebv-induced-lymphoproliferative-disease-and-lytic-viral-replication
#14
Andrea Bilger, Julie Plowshay, Shidong Ma, Dhananjay Nawandar, Elizabeth A Barlow, James C Romero-Masters, Jillian A Bristol, Zhe Li, Ming-Han Tsai, Henri-Jacques Delecluse, Shannon C Kenney
EBV infection causes mononucleosis and is associated with specific subsets of B cell lymphomas. Immunosuppressed patients such as organ transplant recipients are particularly susceptible to EBV-induced lymphoproliferative disease (LPD), which can be fatal. Leflunomide (a drug used to treat rheumatoid arthritis) and its active metabolite teriflunomide (used to treat multiple sclerosis) inhibit de novo pyrimidine synthesis by targeting the cellular dihydroorotate dehydrogenase, thereby decreasing T cell proliferation...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28549714/the-enigmatic-role-of-viruses-in-multiple-sclerosis-molecular-mimicry-or-disturbed-immune-surveillance
#15
REVIEW
Jens Geginat, Moira Paroni, Massimiliano Pagani, Daniela Galimberti, Raffaele De Francesco, Elio Scarpini, Sergio Abrignani
Multiple sclerosis (MS) is a T cell driven autoimmune disease of the central nervous system (CNS). Despite its association with Epstein-Barr Virus (EBV), how viral infections promote MS remains unclear. However, there is increasing evidence that the CNS is continuously surveyed by virus-specific T cells, which protect against reactivating neurotropic viruses. Here, we discuss how viral infections could lead to the breakdown of self-tolerance in genetically predisposed individuals, and how the reactivations of viruses in the CNS could induce the recruitment of both autoaggressive and virus-specific T cell subsets, causing relapses and progressive disability...
May 23, 2017: Trends in Immunology
https://www.readbyqxmd.com/read/28506921/decrease-of-blood-anti-%C3%AE-1-3-galactose-abs-levels-in-multiple-sclerosis-ms-and-clinically-isolated-syndrome-cis-patients
#16
L Le Berre, J Rousse, P-A Gourraud, B-M Imbert-Marcille, A Salama, G Evanno, G Semana, A Nicot, E Dugast, P Guérif, C Adjaoud, T Freour, S Brouard, F Agbalika, R Marignier, D Brassat, D-A Laplaud, E Drouet, V Van Pesch, J-P Soulillou
The etiology of multiple sclerosis (MS) remains elusive. Among the possible causes, the increase of anti-Neu5Gc antibodies during EBV primo-infection of Infectious mononucleosis (IMN) may damage the integrity of the blood-brain barrier facilitating the transfer of EBV-infected B cells and anti-EBV T cell clones in the brain. We investigated the change in titers of anti-Neu5Gc and anti-α1,3 Galactose antibodies in 49 IMN, in 76 MS, and 73 clinically isolated syndrome (CIS) patients, as well as age/gender-matched healthy individuals...
July 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28495131/massive-intracerebral-epstein-barr-virus-reactivation-in-lethal-multiple-sclerosis-relapse-after-natalizumab-withdrawal
#17
Barbara Serafini, Eleonora Scorsi, Barbara Rosicarelli, Valérie Rigau, Eric Thouvenot, Francesca Aloisi
Rebound of disease activity in multiple sclerosis patients after natalizumab withdrawal is a potentially life-threatening event. To verify whether highly destructive inflammation after natalizumab withdrawal is associated with Epstein-Barr virus (EBV) reactivation in central nervous system infiltrating B-lineage cells and cytotoxic immunity, we analyzed post-mortem brain tissue from a patient who died during a fulminating MS relapse following natalizumab withdrawal. Numerous EBV infected B cells/plasma cells and CD8+ T cells infiltrated all white matter lesions; the highest frequency of EBV lytically infected cells and granzyme B+ CD8+ T cells was observed in actively demyelinating lesions...
June 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28388676/epstein-barr-virus-antibodies-in-serum-and-dna-load-in-saliva-are-not-associated-with-radiological-or-clinical-disease-activity-in-patients-with-early-multiple-sclerosis
#18
René M Gieß, Catherina Pfuhl, Janina R Behrens, Ludwig Rasche, Erik Freitag, Nima Khalighy, Carolin Otto, Jens Wuerfel, Alexander U Brandt, Jörg Hofmann, Bettina Eberspächer, Judith Bellmann-Strobl, Friedemann Paul, Klemens Ruprecht
OBJECTIVE: To investigate the association of Epstein-Barr virus (EBV) nuclear antigen-1 (EBNA-1) and viral capsid antigen (VCA) immunoglobulin (Ig)G antibodies in serum as well as EBV DNA load in saliva with radiological and clinical disease activity in patients with clinically isolated syndrome (CIS) and early relapsing-remitting MS (RRMS). METHODS: EBNA-1 and VCA immunoglobulin (Ig)G antibodies were determined in serum of 100 patients with CIS/early RRMS and 60 healthy controls...
2017: PloS One
https://www.readbyqxmd.com/read/28385186/untreated-relapsing-remitting-multiple-sclerosis-patients-show-antibody-production-against-latent-epstein-barr-virus-ebv-antigens-mainly-in-the-periphery-and-innate-immune-il-8-responses-preferentially-in-the-cns
#19
Sofia Sisay, Lorena Lopez-Lozano, Marius Mickunas, Antonio Quiroga-Fernández, Jacqueline Palace, Gary Warnes, Roberto Alvarez-Lafuente, Priyamvada Dua, Ute-Christiane Meier
BACKGROUND: Multiple sclerosis (MS) is an inflammatory and neurodegenerative disorder of the central nervous system (CNS). Reliable biomarkers are urgently needed for its diagnosis and management, and as clues to its pathogenesis, in which EBV is implicated. OBJECTIVE: To measure IgG antibodies against EBV nuclear antigen-1 (EBNA-1) and innate inflammation status in paired serum and cerebrospinal fluid (CSF) samples from untreated relapsing-remitting MS (RRMS) patients...
May 15, 2017: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/28276306/designing-an-effective-vaccine-to-prevent-epstein-barr-virus-associated-diseases-challenges-and-opportunities
#20
Vijayendra Dasari, Kunal H Bhatt, Corey Smith, Rajiv Khanna
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus associated with a number of clinical manifestations. Primary EBV infection in young adolescents often manifests as acute infectious mononucleosis and latent infection is associated with multiple lymphoid and epithelial cancers and autoimmune disorders, particularly multiple sclerosis. Areas covered: Over the last decade, our understanding of pathogenesis and immune regulation of EBV-associated diseases has provided an important platform for the development of novel vaccine formulations...
April 2017: Expert Review of Vaccines
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