ArticleNeurology2015
Epstein-Barr virus genetic variants are associated with multiple sclerosis.
2 registry-linked trialsOpen access · greenAbstract read
In one paragraph
Article in Neurology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 36 papers.
0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.0field-weighted citation impact, top 12% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Interventional Not Pharmacological Study to Investigate the Role of ADA in Multiple Sclerosis PatientsTreated With an Immune-Reconstitution Therapy (2-CdA)
Effects of Ozanimod on Immune-mediated Mechanisms of Neurodegeneration in Multiple Sclerosis - a Preclinical Study
Who cites it
36 citing papers in PubMed, 56 citations in OpenAlex.
- EBV reactivation priming of the peripheral immune system in multiple sclerosis relapse.Nature medicine · 2026Article
- Epstein-Barr Virus and Multiple Sclerosis: Mechanistic Insights into Virus-Driven Autoimmunity.Microorganisms · 2026Review
- Molecular Mimicry by the Tick-Borne Encephalitis Virus E Protein: A Hidden Link to Autoimmunity.International journal of molecular sciences · 2026Article
- EBV genome analysis in multiple sclerosis shows extensive viral diversity and links to autoimmunity.NAR molecular medicine · 2026Article
- EBV Genome Variations and Association With Diseases.Journal of medical virology · 2026Review
- SARS-CoV-2 Spike Protein and Molecular Mimicry: An Immunoinformatic Screen for Cross-Reactive Autoantigen Candidates.International journal of molecular sciences · 2025Article
- A disease-specific convergence of host and Epstein-Barr virus genetics in multiple sclerosis.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Multiple sclerosis and infection: history, EBV, and the search for mechanism.Microbiology and molecular biology reviews : MMBR · 2025Review
- Epstein-Barr virus as a potentiator of autoimmune diseases.Nature reviews. Rheumatology · 2024Review
- Shared and distinct interactions of type 1 and type 2 Epstein-Barr Nuclear Antigen 2 with the human genome.BMC genomics · 2024Article
- Enhanced and cross-reactiveFrontiers in immunology · 2024Article
- Genotypes Distribution of Epstein-Barr Virus among Lymphoma Patients in Ethiopia.International journal of molecular sciences · 2023Article
- Epstein-Barr virus as a leading cause of multiple sclerosis: mechanisms and implications.Nature reviews. Neurology · 2023Review
- The value of Interferon β in multiple sclerosis and novel opportunities for its anti-viral activity: a narrative literature review.Frontiers in immunology · 2023Review
- Epstein-Barr virus infection as potential indicator of the occurrence and clinical presentation of systemic lupus erythematosus.Frontiers in immunology · 2023Article
- Multiple sclerosis genetic and non-genetic factors interact through the transient transcriptome.Scientific reports · 2022Article
- Herpesvirus Infections in KIR2DL2-Positive Multiple Sclerosis Patients: Mechanisms Triggering Autoimmunity.Microorganisms · 2022Article
- Prevention of MS Requires Intervention on the Causes of the Disease: Reconciling Genes, Epigenetics, and Epstein Barr Virus.Frontiers in neurology · 2022Article
- Antibodies from Multiple Sclerosis Brain Identified Epstein-Barr Virus Nuclear Antigen 1 & 2 Epitopes which Are Recognized by Oligoclonal Bands.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- A Case of Double Standard: Sex Differences in Multiple Sclerosis Risk Factors.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 2 institutions in 2 countries.
Rosella MechelliFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Caterina ManzariFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Claudia PolicanoFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Anita AnneseFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Ernesto PicardiFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Renato UmetonFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Arianna FornasieroFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Anna Maria D'ErchiaFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Maria Chiara BuscarinuFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Cristina AgliardiFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Viviana AnnibaliFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Barbara SerafiniFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Barbara RosicarelliFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Silvia RomanoFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Daniela F AngeliniFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Vito A G RiciglianoFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Fabio ButtariFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Luca BattistiniFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Diego CentonzeFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Franca R GueriniFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Sandra D'AlfonsoFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Graziano PesoleFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Marco SalvettiFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy. marco.salvetti@uniroma1.it.
Giovanni RistoriFrom the Centre for Experimental Neurological Therapies (R.M., C.P., R.U., V.A.G.R., A.F., V.A., M.C.B., S.R., M.S., G.R.), S. Andrea Hospital-site, Department of Neuroscience, Mental Health and Sensory Organs, Faculty of Medicine and Psychology, Sapienza University, Rome; Don C. Gnocchi Foundation IRCCS (F.R.G., C.A.), S. Maria Nascente, Milan; Department of Health Sciences (S.D.), Interdisciplinary Research Center of Autoimmune Diseases, Eastern Piedmont University, Novara; Clinica Neurologica (F.B., D.C.), Dipartimento di Medicina dei Sistemi, University of Tor Vergata, Rome; Department of Cell Biology and Neuroscience (B.S., B.R.), Istituto Superiore di Sanità, Rome; Department of Bioscience, Biotechnology and Biopharmaceutics (C.M., A.A., A.M.D., E.P., G.P.) University of Bari "Aldo Moro"; Institute of Biomembranes and Bioenergetics (G.P.), CNR, Bari; and Neuroimmunology Unit (D.F.A., L.B.), Fondazione Santa Lucia (I.R.C.C.S.), Rome, Italy.
Institute of Biomembranes, Bioenergetics and Molecular Biotechnologies · ITPiedmont University · US
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveWe analyzed the Epstein-Barr nuclear antigen 2 (EBNA2) gene, which contains the most variable region of the viral genome, in persons with multiple sclerosis (MS) and control subjects to verify whether virus genetic variants are involved in disease development.
methodsA seminested PCR approach and Sanger sequencing were used to analyze EBNA2 in 53 patients and 38 matched healthy donors (HDs). High-throughput sequencing by Illumina MiSeq was also applied in a subgroup of donors (17 patients and 17 HDs). Patients underwent gadolinium-enhanced MRI and human leucocyte antigen typing.
resultsMS risk significantly correlated with an excess of 1.2 allele (odds ratio [OR] = 5.13; 95% confidence interval [CI] 1.84-14.32; p = 0.016) and underrepresentation of 1.3B allele (OR = 0.23; 95% CI 0.08-0.51; p = 0.0006). We identified new genetic variants, mostly 1.2 allele- and MS-associated (especially amino acid variation at position 245; OR = 9.4; 95% CI 1.19-78.72; p = 0.0123). In all cases, the consensus sequence from deep sequencing confirmed Sanger sequencing (including the cosegregation of newly identified variants with known EBNA2 alleles) and showed that the extent of genotype intraindividual variability was higher than expected: rare EBNA2 variants were detected in all HDs and patients with MS (range 1-17 and 3-19, respectively). EBNA2 variants did not seem to correlate with human leucocyte antigen typing or clinical/MRI features.
conclusionsOur study unveils a strong association between Epstein-Barr virus genomic variants and MS, reinforcing the idea that Epstein-Barr virus contributes to disease development.
Indexed as
Genetic VariationAdultAllelesCase-Control StudiesEpstein-Barr Virus Nuclear AntigensGenotypeHerpesvirus 4, HumanHistocompatibility TestingHLA AntigensHumansMaleMultiple SclerosisYoung AdultEpstein-Barr Virus Nuclear AntigensHLA Antigens
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Registered trials
NCT04121065ClinicalTrials.gov
NCT05245344ClinicalTrials.gov
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