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EBV and multiple sclerosis

Elisenda Alari-Pahissa, Antía Moreira, Ana Zabalza, Roberto Alvarez-Lafuente, Elvira Munteis, Andrea Vera, Rafael Arroyo, Jose C Alvarez-Cermeño, Luisa Maria Villar, Miguel López-Botet, Jose E Martínez-Rodríguez
BACKGROUND AND PURPOSE: Cytomegalovirus (CMV) infection has been recently associated with a lower multiple sclerosis (MS) susceptibility, remaining controversial whether it has a protective role or is merely an epiphenomenon related to westernization and early-life viral infections. We aimed to evaluate whether CMV serostatus may differ in early MS as compared to non-early MS patients, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses...
March 12, 2018: European Journal of Neurology: the Official Journal of the European Federation of Neurological Societies
Marco Bo, Magdalena Niegowska, Giannina Arru, Elia Sechi, Sara Mariotto, Chiara Mancinelli, Alessia Farinazzo, Daniela Alberti, Alberto Gajofatto, Sergio Ferrari, Ruggero Capra, Salvatore Monaco, GianPietro Sechi, Leonardo A Sechi
Epstein-Barr virus (EBV) is the main environmental agent associated to neuromyelitis optica spectrum disorder (NMOSD). Following to studies reporting an increased prevalence of antibodies against peptides derived from Mycobacterium avium subsp. paratuberculosis (MAP) homologous to EBV and human epitopes (MBP85-98 , IRF5424-434 ) in multiple sclerosis (MS), we investigated whether seroreactivity to these antigens display a NMOSD-specific pattern. The sera of 34 NMOSD patients showed elevated levels of antibodies against MAP and MBP compared to healthy controls (44% vs...
February 28, 2018: Journal of Neuroimmunology
Nataša Beader, Branko Kolarić, Domagoj Slačanac, Irena Tabain, Tatjana Vilibić-Čavlek
BACKGROUND: The Epstein-Barr virus (EBV) is one of the most common viruses found in humans, causing lifelong infection in up to 95% of the world population. OBJECTIVES: To analyze the seroprevalence of EBV infection in different population groups in Croatia. METHODS: During a 2 year period (2015-2016), a total of 2022 consecutive serum samples collected from Croatian residents were tested for the presence of EBV-specific viral capsid antigen (VCA) immunoglobulin M (IgM) and IgG antibodies using an enzyme-linked immunoassay...
February 2018: Israel Medical Association Journal: IMAJ
Asma Hassani, John R Corboy, Suhail Al-Salam, Gulfaraz Khan
Multiple sclerosis (MS) is a chronic neuroinflammatory condition of the central nervous system (CNS). It is a major cause of neurological disability in young adults, particularly women. What triggers the destruction of myelin sheaths covering nerve fibres is unknown. Both genetic and infectious agents have been implicated. Of the infectious agents, Epstein-Barr virus (EBV), a common herpesvirus, has the strongest epidemiological and serological evidence. However, the presence of EBV in the CNS and demonstration of the underlying mechanism(s) linking EBV to the pathogenesis of MS remain to be elucidated...
2018: PloS One
Amy M Lavery, Bradley N Collins, Amy T Waldman, Chantelle N Hart, Amit Bar-Or, Ruth Ann Marrie, Douglas Arnold, Julia O'Mahony, Brenda Banwell
BACKGROUND: Pediatric acquired demyelinating syndromes (ADSs) are monophasic (mono-ADS) in 70% of cases and represent the first attack of multiple sclerosis (MS) in 30%. Secondhand tobacco smoke (SHS) exposure has been implicated as a risk factor for adult-onset MS. Little is known about whether SHS presents an additive risk beyond genetic factors and other environmental exposures associated with pediatric MS. METHODS: This study examined SHS exposure in 216 children with mono-ADS and 81 children with MS...
January 1, 2018: Multiple Sclerosis: Clinical and Laboratory Research
Caterina Veroni, Barbara Serafini, Barbara Rosicarelli, Corrado Fagnani, Francesca Aloisi
BACKGROUND: It is debated whether multiple sclerosis (MS) might result from an immunopathological response toward an active Epstein-Barr virus (EBV) infection brought into the central nervous system (CNS) by immigrating B cells. Based on this model, a relationship should exist between the local immune milieu and EBV infection status in the MS brain. To test this hypothesis, we analyzed expression of viral and cellular genes in brain-infiltrating immune cells. METHODS: Twenty-three postmortem snap-frozen brain tissue blocks from 11 patients with progressive MS were selected based on good RNA quality and prominent immune cell infiltration...
January 16, 2018: Journal of Neuroinflammation
Yuan Zhou, Ming Chen, Steve Simpson, Robyn M Lucas, Jac C Charlesworth, Nicholas Blackburn, Ingrid van der Mei, Anne-Louise Ponsonby, Bruce V Taylor
Despite extensive studies focusing on the changes in expression of microRNAs (miRNAs) in multiple sclerosis (MS) compared to healthy controls, few studies have evaluated the association of genetic variants of miRNAs with MS clinical course. We investigated whether a functional polymorphism in the MS associated miR-146a gene predicted clinical course (hazard of conversion to MS and of relapse, and annualized change in disability), using a longitudinal cohort study of persons with a first demyelinating event followed up to their 5-year review...
November 10, 2017: Neurological Sciences
Awatef M Awwad, Nesrine F Hanafi, Ghada A Achmawi, Amira M Naguib
Multiple sclerosis (MS) is the most common inflammatory autoimmune CNS disease, with unknown etiology. We aimed to determine the coexistence of MS with antibodies to Epstein-Barr virus and its gene sequences (EBNA1 and BHRF1). The study included 60 MS patients and 60 control subjects. Serum samples were processed by ELISA for detection of EBV antibodies, and latent EBV genes were determined by Real Time PCR in blood samples. While 18 (30%) MS cases had anti- EBV IgM antibodies, all controls were free. For IgG, no difference was noted (cases 96...
January 2017: Egyptian Journal of Immunology
Julio Alonso-Padilla, Esther M Lafuente, Pedro A Reche
Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt's lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes...
2017: Journal of Immunology Research
Klemens Ruprecht, Brigitte Wildemann, Sven Jarius
BACKGROUND: Patients with multiple sclerosis (MS) frequently have an intrathecal production of antibodies to different common viruses, which can be detected by elevated antiviral antibody indices (AIs). There is a strong and consistent association of MS and Epstein-Barr virus (EBV) infection. OBJECTIVE: To systematically compare the frequencies of intrathecal antibody production to EBV, measles virus, rubella virus, varicella zoster virus (VZV) and herpes simplex virus (HSV) in patients with MS...
November 2, 2017: Journal of Neurology
Walter Fierz
Viruses are able to interfere with the immune system by docking to receptors on host cells that are important for proper functioning of the immune system. A well-known example is the human immunodeficiency virus that uses CD4 cell surface molecules to enter host lymphocytes and thereby deleteriously destroying the helper cell population of the immune system. A more complicated mechanism is seen in multiple sclerosis (MS) where human herpes virus-6A (HHV-6A) infects astrocytes by docking to the CD46 surface receptor...
2017: Frontiers in Immunology
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...
September 26, 2017: Neurology
Maria T Cencioni, Roberta Magliozzi, Richard Nicholas, Rehiana Ali, Omar Malik, Richard Reynolds, Giovanna Borsellino, Luca Battistini, Paolo A Muraro
Growing evidence points to a deregulated response to Epstein-Barr virus (EBV) in the central nervous system of patients with multiple sclerosis (MS) as a possible cause of disease. We have investigated the response of a subpopulation of effector CD8+ T cells to EBV in 36 healthy donors and in 35 patients with MS 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 immunoglobulin-like transcript 2 (ILT2)...
December 2017: Immunology
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
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
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
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
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
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...
September 2017: Acta Neuropathologica
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
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