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Absence of Epstein-Barr virus seronegativity in a large cohort of patients with early multiple sclerosis
ECTRIMS Online Library. Ruprecht K. Oct 12, 2018; 232073
Klemens Ruprecht
Klemens Ruprecht
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Abstract: 320

Type: Scientific Session

Abstract Category: N/A

Background: The strong association of multiple sclerosis (MS) and Epstein-Barr virus (EBV) infection raises the question whether there might be EBV seronegative patients with MS at all.
Objective: To determine the rate of EBV seronegativity in a large and well-characterized cohort of patients with a clinically isolated syndrome (CIS) or early relapsing-remitting (RR)MS.
Methods: Epstein-Barr nuclear antigen-1 (EBNA-1) antibodies were measured by a chemiluminescent assay (CLIA) in serum samples of 901 patients (median [interquartile range] age 33 [27-41] years, 69.9% females) with a CIS (n = 380) or early RRMS (n = 521) from the German National MS cohort. In EBNA-1 antibody seronegative patients, antibodies to the EBV viral capsid antigen (VCA) were measured by CLIA. EBNA-1 and VCA antibody double seronegative patients were analysed by an EBV immunoblot.
Results: Antibodies to EBNA-1 were detected in 839 of 901 patients with CIS/RRMS. Of the 62 EBNA-1 antibody seronegative patients, 45 had antibodies to VCA. Of the 17 remaining patients, all had antibodies to EBV as detected by EBV immunoblot. Thus, all 901 (100%) patients with CIS/RRMS investigated in this study were EBV seropositive.
Conclusions: The absence of EBV seronegativity in this large cohort of patients with early MS provides further evidence for a crucial role of EBV in MS and suggests that a negative EBV serology in a patient with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.
Disclosure: SA reports no disclosures.
BE reports no disclosures.
BA received travel grants from Novartis, not related to this work.
NH reports no disclosures.
GA reports no disclosures.
IRK reports no disclosures.
M-MH received travel expenses from Bayer Health Care and honoraria for an advisory board from Merck Serono GmbH.
LA reports no disclosures.
FL serves as an advisory board member for Roche Pharma and has received travel grants from Teva Pharma.
SG reports no disclosures.
LK received compensation for serving on scientific advisory boards (Genzyme, Novartis Pharma); speaker honoraria and travel support (CSL Behring, Merck Serono, Roche, Novartis Pharma); research support (Biogen, Novartis Pharma).
SGM received honoraria for lecturing, travel expenses for attending meetings, and/or financial research support from Almirall, Bayer Health Care, Biogen, Diamed, Fresenius Medical Care, Genzyme, Merck Serono, Novartis, Novo Nordisk, ONO Pharma, Roche, Sanofi-Aventis and Teva.
BT received personal speaker honoraria and consultancy fees as a speaker and advisor from Bayer Healthcare, Biogen, CSL Behring, GRIFOLS, Merck Serono, Novartis, Octapharma, Roche, Sanofi Genzyme, TEVA und UCB Pharma. His University received unrestricted research grants from Biogen-idec, Novartis, TEVA, Bayer Healthcare, CSL-Behring, GRIFOLS, Octapharma, Sanofi Genzyme und UCB Pharma; none related to this work.
MuS received travel support to attend scientific meetings from Biogen, Merck Serono, Novartis and TEVA. She received, through her institution, an unrestricted research grant from Novartis, unrelated to this work. She has received funding, through TRM Leipzig, from the German Federal Ministry of Education and Research (BMBF).
FTB received personal compensation for speaking and attending advisory boards from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis, Teva and Roche; financial support, through his institution, to attend scientific meetings or for investigator initiated studies from Actelion, Bayer, Biogen, Genzyme, Merck, Novartis and Teva.
HT received speaker honoraria from Bayer, Biogen, Fresenius, Genzyme, Merck, Novartis, Roche, Siemens, Teva; serves as section editor for the Journal of Neurology, Psychiatry, and Brain Research; and receives research support from Fresenius, Genzyme, Merck, and Novartis; none related to this work.
TK received travel expenses and personal compensations from Bayer Healthcare, Teva Pharma, Merck-Serono, Novartis, Sanofi-Aventis/Genzyme, Roche and Biogen as well as grant support from Bayer-Schering AG, Novartis and Chugai Pharma; none related to this work.
MS received honoraria for scientific lectures or consultancy from Bayer Healthcare, Biogen, Baxter/Baxalta, CSL Behring, Euroimmune, Grifols, Merck-Serono, Novartis, Roche, Sanofi-Aventis, and Teva. His institution received research support from Bayer Healthcare, Biogen Idec, Genzyme, Merck-Serono, Novartis, and Teva; none related to this work.
CH received research grants and speaker honoraria from Biogen, Genzyme, Roche, and Merck; none related to this work.
BW received grants from the German Ministry of Education and Research, Dietmar Hopp Foundation and Klaus Tschira Foundation, grants and personal fees from Biogen, Merck Serono, Sanofi Genzyme, Novartis pharmaceuticals, Teva Pharma, and personal fees from Bayer Healthcare; none related to this work.
FP serves on the scientific advisory board for Novartis; received speaker honoraria and travel funding from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Merck Serono, Alexion, Chugai, MedImmune, and Shire; is an academic editor for PLoS ONE; is an associate editor for Neurology® Neuroimmunology & Neuroinflammation; consulted for SanofiGenzyme, Biogen Idec, MedImmune, Shire, and Alexion; and received research support from Bayer, Novartis, Biogen Idec, Teva, Sanofi-Aventis/Genzyme, Alexion, Merck Serono, German Research Council, Werth Stiftung of the City of Cologne, German Ministry of Education and Research, Arthur Arnstein Stiftung Berlin, EU FP7 Framework Program, Arthur Arnstein Foundation Berlin, Guthy Jackson Charitable Foundation, and National Multiple Sclerosis of the USA; none related to this work.
AB served on scientific advisory boards of Merck Serono, Biogen, Novartis, Teva, Sanofi/ Genzyme, and Roche; received travel funding and speaker honoraria from Merck Serono, Biogen, Novartis, Teva, Bayer, and Sanofi/Genzyme; and consulted for Merck Serono, Biogen, and Novartis.
CW received personal fees for consulting: Biogen, Novartis (none since 8/2016). Consulting for the European Medicines Agency, and the Institute for Quality and Efficiency in Health Care, Germany, none related to this work.
FW received honoraria from Genzyme, Novartis TEVA and Biogen for speaking or for serving on a scientific advisory board, a travel grant for the attention of a scientific meeting from Merck-Serono and Novartis and grant support from Merck-Serono, Novartis and from the Federal Ministry of Education and Research (BMBF, Projects Biobanking and Omics in ControlMS as part of the Competence Network Multiple Sclerosis).
RAL received Research Support and/or personal compensation for activities with Bayer Health Care, Biogen, Genzyme/Sanofi, Merck, Novartis Pharma, Roche, and TEVA Pharma; none related to this work.
UZ received speaker honoraria and/or travel compensation from Biogen Idec GmbH, Bayer Vital GmbH, Bristol Myers Squibb GmbH, CorTec GmbH, Medtronic GmbH, and grants from Biogen Idec GmbH, Servier, and Janssen Pharmaceuticals NV; none related to this work.
UKZ received speaker fees from Aventis, Almirall, Biogen, Bayer, Merck, Novartis, Roche, and Teva.
FZ received funds for scientific consultation or research of DFG, BMBF, Novartis, Octapharma, Merck Serono, ONO Pharma, Biogen, Genzyme, and Sanofi Aventis within the past 3 years.
HW receives honoraria for acting as a member of Scientific Advisory Boards and as a consultant for Biogen, Evgen, MedDay Pharmaceuticals, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, as well as speaker honoraria and travel support from Alexion, Biogen, Cognomed, F. Hoffmann-La Roche Ltd., Gemeinnützige Hertie-Stiftung, Merck Serono, Novartis, Roche Pharma AG, Sanofi-Genzyme, TEVA, and WebMD Global. Prof. Wiendl is acting as a paid consultant for Abbvie, Actelion, Biogen, IGES, Novartis, Roche, Sanofi-Genzyme, and the Swiss Multiple Sclerosis Society. His research is funded by the BMBF, DFG, Else Kröner Fresenius Foundation, Fresenius Foundation, Hertie Foundation, NRW Ministry of Education and Research, Interdisciplinary Center for Clinical Studies (IZKF) Muenster and RE Children's Foundation, Biogen GmbH, GlaxoSmithKline GmbH, and Roche Pharma AG, Sanofi-Genzyme.
BH served on scientific advisory boards for F. Hoffmann-La Roche Ltd, Novartis, Bayer AG, and Genentech; he has served as DMSC member for AllergyCare and TG Therapeutics; he or his institution have received speaker honoraria from Biogen Idec, Teva Neuroscience, Merck Serono, Medimmune, Novartis, Desitin, and F. Hoffmann-La Roche Ltd; his institution has received research support from Chugai Pharmaceuticals; holds part of two patents; one for the detection of antibodies and T cells against KIR4.1 in a subpopulation of MS patients and one for genetic determinants of neutralizing antibodies to interferon β during the last 3 years.
RG serves on scientific advisory boards for Teva Pharmaceutical Industries Ltd., Biogen Idec, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen Idec, Teva Pharmaceutical Industries Ltd., Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; and receives researc

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