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EBV and multiple sclerosis

Matthew M Dooley, Samantha L de Gannes, Kristi A Fu, J William Lindsey
Multiple sclerosis (MS) is associated with Epstein-Barr virus (EBV) infection, and the antibody response to EBV is reported to be increased in MS. EBV contains multiple antigens, and only a few have been investigated. Our hypothesis is that MS patients will have an increased antibody response to only selected EBV antigens. We used immunoprecipitation and quantitative mass spectrometry to identify candidate EBV antigens. We then measured the antibody response to 10 individual EBV proteins with quantitative ELISA...
October 15, 2016: Journal of Neuroimmunology
Kjetil Bjørnevik, Trond Riise, Inger Bostrom, Llaria Casetta, Marianna Cortese, Enrico Granieri, Trygve Holmøy, Margitta T Kampman, Anne-Marie Landtblom, Sandra Magalhaes, Maura Pugliatti, Christina Wolfson, Kjell-Morten Myhr
BACKGROUND: Results from previous studies on a possible interaction between smoking and Epstein-Barr virus (EBV) in the risk of multiple sclerosis (MS) are conflicting. OBJECTIVES: To examine the interaction between smoking and infectious mononucleosis (IM) in the risk of MS. METHODS: Within the case-control study on Environmental Factors In Multiple Sclerosis (EnvIMS), 1904 MS patients and 3694 population-based frequency-matched healthy controls from Norway, Italy, and Sweden reported on prior exposure to smoking and history of IM...
September 23, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Matteo Chiara, Caterina Manzari, Claudia Lionetti, Rosella Mechelli, Eleni Anastasiadou, Maria Chiara Buscarinu, Giovanni Ristori, Marco Salvetti, Ernesto Picardi, Anna Maria D'Erchia, Graziano Pesole, David S Horner
Epstein-Barr virus (EBV) latently infects the majority of the human population and is implicated as a causal or contributory factor in numerous diseases. We sequenced 27 complete EBV genomes from a cohort of Multiple Sclerosis (MS) patients and healthy controls from Italy, although no variants showed a statistically significant association with MS. Taking advantage of the availability of ~130 EBV genomes with known geographical origins, we reveal a striking geographic distribution of EBV sub-populations with distinct allele frequency distributions...
September 15, 2016: Genome Biology and Evolution
Emmanuelle Waubant, Anne-Louise Ponsonby, Maura Pugliatti, Heather Hanwell, Ellen M Mowry, Rogier Q Hintzen
The onset of multiple sclerosis (MS) occurs in childhood in about 5% of all patients with MS. The disease in adults has a complex genetic and environmental inheritability. One of the main risk factors, also confirmed in pediatric MS, is HLA DRB1*1501 In addition to genetic factors, a large part of disease susceptibility in adults is conferred by environmental risk factors such as low vitamin D status, exposure to cigarette smoking, and remote Epstein-Barr virus (EBV) infection. In children, both exposure to cigarette smoking and prior EBV infection have been reported consistently as risk factors for MS...
August 30, 2016: Neurology
Amandine Mathias, Guillaume Perriard, Mathieu Canales, Charlotte Soneson, Mauro Delorenzi, Myriam Schluep, Renaud A Du Pasquier
BACKGROUND: Multiple sclerosis (MS) is thought to be T cell mediated but the mechanisms eliciting such a dysregulated adaptative immune response remain enigmatic. OBJECTIVE: To examine the activation profile of antigen-presenting cells (APCs) in MS. METHODS: A total of 98 study subjects were enrolled including patients suffering from relapsing-remitting, secondary- and primary-progressive (PP) MS, other inflammatory neurological diseases, and healthy controls...
August 8, 2016: Multiple Sclerosis: Clinical and Laboratory Research
S Anwar Jagessar, Inge R Holtman, Sam Hofman, Elena Morandi, Nicole Heijmans, Jon D Laman, Bruno Gran, Bart W Faber, Sander I van Kasteren, Bart J L Eggen, Bert A 't Hart
EBV is the major infectious environmental risk factor for multiple sclerosis (MS), but the underlying mechanisms remain obscure. Patient studies do not allow manipulation in vivo. We used the experimental autoimmune encephalomyelitis (EAE) models in the common marmoset and rhesus monkey to model the association of EBV and MS. We report that B cells infected with EBV-related lymphocryptovirus (LCV) are requisite APCs for MHC-E-restricted autoaggressive effector memory CTLs specific for the immunodominant epitope 40-48 of myelin oligodendrocyte glycoprotein (MOG)...
August 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Ludwig Schlemm, René Markus Giess, Ludwig Rasche, Catherina Pfuhl, Katharina Wakonig, Janina Ruth Behrens, Carmen Scheibenbogen, Judith Bellmann-Strobl, Friedemann Paul, Ulf Reimer, Klemens Ruprecht
We analyzed the fine specificity of antibodies to Epstein-Barr nuclear antigen-2 (EBNA-2) and other Epstein-Barr virus (EBV) proteins in 29 patients with clinically isolated syndrome (CIS, the first clinical manifestation of multiple sclerosis [MS]) and 29 controls with a peptide microarray containing 117 overlapping peptides representing the full-length EBNA-2 protein and 71 peptides from 8 further EBV proteins. While EBV peptide antibodies were elevated in CIS, suggesting that EBV contributes to MS early during disease development, they discriminated groups only slightly better than EBNA-1 antibodies...
August 15, 2016: Journal of Neuroimmunology
Giuseppe Mameli, Eleonora Cocco, Jessica Frau, Giannina Arru, Elisa Caggiu, Maria Giovanna Marrosu, Leonardo A Sechi
Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs)...
2016: Scientific Reports
Egil Røsjø, Andreas Lossius, Nada Abdelmagid, Jonas C Lindstrøm, Margitta T Kampman, Lone Jørgensen, Peter Sundström, Tomas Olsson, Linn H Steffensen, Øivind Torkildsen, Trygve Holmøy
BACKGROUND: Elevated antibody levels against Epstein-Barr virus (EBV) and a poor vitamin D status are environmental factors that may interact in relapsing-remitting multiple sclerosis (RRMS) aetiology. OBJECTIVES: To examine effects of high-dose oral vitamin D3 supplementation on antibody levels against EBV nuclear antigen 1 (EBNA1) in RRMS. METHODS: Serum 25-hydroxyvitamin D3 (25(OH)D) and immunoglobulin G antibody levels against EBNA1 (whole protein and amino acid 385-420 fragment), EBV viral capsid antigen (VCA), cytomegalovirus (CMV) and varicella zoster virus (VZV) were measured in 68 RRMS patients enrolled in a 96-week randomised double-blinded placebo-controlled clinical trial of oral vitamin D3 supplementation (20,000 IU/week) (NCT00785473)...
June 20, 2016: Multiple Sclerosis: Clinical and Laboratory Research
Giuseppe Mameli, Giannina Arru, Elisa Caggiu, Magdalena Niegowska, Stefania Leoni, Giordano Madeddu, Sergio Babudieri, Gian Pietro Sechi, Leonardo A Sechi
MicroRNAs fine-tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti-EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR-155, miR-26a, miR-132, miR-146a and Th1/Th17 cytokines expression was detected by RT-real time PCR; moreover anti-EBNA1 and VCA IgG titres were measured by ELISA...
2016: PloS One
Fabiana Rizzo, Elena Giacomini, Rosella Mechelli, Maria Chiara Buscarinu, Marco Salvetti, Martina Severa, Eliana Marina Coccia
Growing evidences put B lymphocytes on a central stage in Multiple sclerosis (MS) immunopathology. While investigating the effects of Interferon (IFN)-β therapy, one of the most used first-line disease-modifying drugs for the treatment of Relapsing-Remitting MS (RRMS), in circulating B cell subpopulations we found a specific and dramatic decrease of CD27(+) memory B cells. Interestingly, memory B cells are considered a population with a great disease-driving relevance in MS and resulted to be also target of B cell depleting therapies...
June 6, 2016: Immunology and Cell Biology
Armando Sena, Carlos Capela, Véronique Ferret-Sena, Kassandra L Munger, Alberto Ascherio, Gustavo Suarez
No abstract text is available yet for this article.
May 24, 2016: Neurology
Carolin Otto, Jörg Hofmann, Klemens Ruprecht
Patients with multiple sclerosis (MS), a chronic inflammatory disease of the central nervous system (CNS), typically have an intrathecal synthesis of immunoglobulin (Ig)G. Intrathecal IgG is produced by B lineage cells that entered the CNS, but why and when these cells invade the CNS of patients with MS is unknown. The intrathecal IgG response in patients with MS is polyspecific and part of it is directed against different common viruses (e.g. measles virus, rubella virus, varicella zoster virus). Strong and consistent evidence suggests an association of MS and Epstein-Barr virus (EBV) infection and EBV seroprevalence in patients with MS is practically 100%...
June 2016: Medical Hypotheses
Marie Wunsch, Christopher Hohmann, Bianca Milles, Christina Rostermund, Paul V Lehmann, Michael Schroeter, Antonios Bayas, Jochen Ulzheimer, Mathias Mäurer, Süleyman Ergün, Stefanie Kuerten
There is a largely divergent body of literature regarding the relationship between Epstein-Barr virus (EBV) infection and brain inflammation in multiple sclerosis (MS). Here, we tested MS patients during relapse (n = 11) and in remission (n = 19) in addition to n = 22 healthy controls to study the correlation between the EBV- and brain-specific B cell response in the blood by enzyme-linked immunospot (ELISPOT) and enzyme-linked immunosorbent assay (ELISA). Cytomegalovirus (CMV) was used as a control antigen tested in n = 16 MS patients during relapse and in n = 35 patients in remission...
April 2016: Viruses
E Carreon-Guarnizo, E Andreu-Reinon, M Cerdan-Sanchez, R Carrasco-Torres, R Hernandez-Clares, L Prieto-Valiente, C Garcia-Escriba, A Sola-Roca, M E Martinez-Andreu, M A Miralles Gonzalez-Conde, J J Martin-Fernandez, J E Meca-Lallana
INTRODUCTION: Multiple sclerosis (MS) is a demyelinating inflammatory disease of the central nervous system with immune-mediated pathogenesis. Recent research points to an increase in its prevalence, and a number of studies relate Epstein-Barr virus (EBV) with its aetiology. AIMS: This study seeks to analyse the prevalence of MS in the Region of Murcia, and includes a description of the clinical characteristics at the time of onset of the disease, and of the EBV serological status of patients with MS...
May 1, 2016: Revista de Neurologia
Anette Draborg, Jose M G Izarzugaza, Gunnar Houen
PURPOSE OF REVIEW: Systemic lupus erythematosus (SLE) is caused by a combination of genetic and acquired immunodeficiencies and environmental factors including infections. An association with Epstein-Barr virus (EBV) has been established by numerous studies over the past decades. Here, we review recent experimental studies on EBV, and present our integrated theory of SLE development. RECENT FINDINGS: SLE patients have dysfunctional control of EBV infection resulting in frequent reactivations and disease progression...
July 2016: Current Opinion in Rheumatology
Pooja Adtani, Narasimhan Malathi
CONTEXT: Pathogenesis of autoimmune diseases (AD) is one of a multifactorial milieu. A genetic predisposition, an immune system failure, hormonal imbalance and environmental factors play important roles. Among the many environmental factors, the role of infection is gaining importance in the pathogenesis of various autoimmune disorders; among them, Epstein-Barr virus (EBV) plays a pivotal role. Literature states an association of various AD with EBV namely multiple sclerosis, autoimmune thyroiditis, systemic lupus erythematous, oral lichen planus (OLP), rheumatoid arthritis (RA), autoimmune hepatitis, Sjögren's syndrome and Kawasaki disease; among these, the most commonly occurring are OLP and RA...
September 2015: Journal of Oral and Maxillofacial Pathology: JOMFP
Giuseppe Mameli, Eleonora Cocco, Jessica Frau, Maria Giovanna Marrosu, Leonardo Antonio Sechi
Mycobacterium avium subsp. paratuberculosis (MAP) and Epstein-Barr virus (EBV) epitopes elicit a consistent humoral response in serum of multiple sclerosis patients, but the cross reactivity against the homologous myelin basic protein (MBP) and human interferon regulatory factor 5 (IRF5) has not been searched within the Cerebral Spinal Fluid (CSF). We evaluated in sera and CSF of patients with MS and with other neurological diseases (OND) the humoral response against EBV/MAP peptides and the IRF5/MBP. Our data showed that EBV and MAP peptides are able to induce a specific humoral immune response in MS patients compared to OND controls both in serum and in CSF...
2016: Scientific Reports
Monika Tschochner, Shay Leary, Don Cooper, Kaija Strautins, Abha Chopra, Hayley Clark, Linda Choo, David Dunn, Ian James, William M Carroll, Allan G Kermode, David Nolan
BACKGROUND: Epstein-Barr virus (EBV) infection represents a major environmental risk factor for multiple sclerosis (MS), with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1)-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome...
2016: PloS One
Yuan Zhou, Gu Zhu, Jac C Charlesworth, Steve Simpson, Rohina Rubicz, Harald Hh Göring, Nikolaos A Patsopoulos, Caroline Laverty, Feitong Wu, Anjali Henders, Jonathan J Ellis, Ingrid van der Mei, Grant W Montgomery, John Blangero, Joanne E Curran, Matthew P Johnson, Nicholas G Martin, Dale R Nyholt, Bruce V Taylor
BACKGROUND: Infection with the Epstein-Barr virus (EBV) is associated with an increased risk of multiple sclerosis (MS). OBJECTIVE: We sought genetic loci influencing EBV nuclear antigen-1 (EBNA-1) IgG titers and hypothesized that they may play a role in MS risk. METHODS: We performed a genome-wide association study (GWAS) of anti-EBNA-1 IgG titers in 3599 individuals from an unselected twin family cohort, followed by a meta-analysis with data from an independent EBNA-1 GWAS...
January 27, 2016: Multiple Sclerosis: Clinical and Laboratory Research
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