Cited by 119Multiple Sclerosis Research StudiesViral-associated cancers and disordersCytomegalovirus and herpesvirus research

Complete Epstein-Barr virus seropositivity in a large cohort of patients with early multiple sclerosis

Open access
Abrahamyan, Sargis, Eberspächer, Bettina, Hoshi, Muna-Miriam, Aly, Lilian, Luessi, Felix, Groppa, Sergiu, Klotz, Luisa, Meuth, Sven G +21 more·2020·Journal of Neurology, Neurosurgery & Psychiatry

Abstract

Objective: To determine the prevalence of antibodies to Epstein-Barr virus (EBV) in a large cohort of patients with early multiple sclerosis (MS). Methods: Serum samples were collected from 901 patients with a clinically isolated syndrome (CIS) or early relapsing–remitting multiple sclerosis (RRMS) participating in the German National MS cohort, a prospective cohort of patients with early MS with stringent inclusion criteria. Epstein-Barr nuclear antigen (EBNA)-1 and viral capsid antigen (VCA) antibodies were measured in diluted sera by chemiluminescence immunoassays (CLIAs). Sera of EBNA-1 and VCA antibody-negative patients were retested undiluted by an EBV IgG immunoblot. For comparison, we retrospectively analysed the EBV seroprevalence across different age cohorts, ranging from 0 to >80 years, in a large hospital population (N=16 163) from Berlin/Northern Germany. Results: EBNA-1 antibodies were detected by CLIA in 839 of 901 patients with CIS/RRMS. Of the 62 patients without EBNA-1 antibodies, 45 had antibodies to VCA as detected by CLIA. In all of the remaining 17 patients, antibodies to EBV were detected by immunoblot. Altogether, 901 of 901 (100%) patients with CIS/RRMS were EBV-seropositive. EBV seropositivity increased with age in the hospital population but did not reach 100% in any of the investigated age cohorts. Conclusion: The complete EBV seropositivity in this large cohort of patients with early MS strengthens the evidence for a role of EBV in MS. It also suggests that a negative EBV serology in patients with suspected inflammatory central nervous system disease should alert clinicians to consider diagnoses other than MS.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1136/jnnp-2020-322941

Cites

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

No references could be resolved yet.

Research works printed but not linked: 26

  1. [1]Ascherio A, Munger KL Environmental risk factors for multiple sclerosis. Part I: the role of infection. Ann Neurol 2007; 61: 288– 99. 10.1002/ana.21117 17444504 · DOI
  2. [2]Ascherio A, Munger KL, Lünemann JD The initiation and prevention of multiple sclerosis. Nat Rev Neurol 2012; 8: 602– 12. 10.1038/nrneurol.2012.198 23045241 PMC4467212 · DOI
  3. [3]Belbasis L, Bellou V, Evangelou E, et al Environmental risk factors and multiple sclerosis: an umbrella review of systematic reviews and meta-analyses. Lancet Neurol 2015; 14: 263– 73. 10.1016/S1474-4422(14)70267-4 25662901 · DOI
  4. [4]Ascherio A, Munger KL Epidemiology of multiple sclerosis: from risk factors to Prevention-An update. Semin Neurol 2016; 36: 103– 14. 10.1055/s-0036-1579693 27116717 · DOI
  5. [5]Deuschle K, Hofmann J, Otto C, et al Are there Epstein-Barr virus seronegative patients with multiple sclerosis? Mult Scler 2013; 19: 1242– 3. 10.1177/1352458512472751 23307904 · DOI
  6. [6]Goodin DS The causal cascade to multiple sclerosis: a model for MS pathogenesis. PLoS One 2009; 4: e4565. 10.1371/journal.pone.0004565 19242548 PMC2644781 · DOI
  7. [7]Pakpoor J, Disanto G, Gerber JE, et al The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scler 2013; 19: 162– 6. 10.1177/1352458512449682 22740437 · DOI
  8. [8]Almohmeed YH, Avenell A, Aucott L, et al Systematic review and meta-analysis of the sero-epidemiological association between Epstein Barr virus and multiple sclerosis. PLoS One 2013; 8: e61110. 10.1371/journal.pone.0061110 23585874 PMC3621759 · DOI
  9. [9]Horakova D, Zivadinov R, Weinstock-Guttman B, et al Environmental factors associated with disease progression after the first demyelinating event: results from the multi-center set study. PLoS One 2013; 8: e53996. 10.1371/journal.pone.0053996 23320113 PMC3540021 · DOI
  10. [10]Dobson R, Kuhle J, Middeldorp J, et al Epstein-Barr-negative MS: a true phenomenon? Neurol Neuroimmunol Neuroinflamm 2017; 4: e318. 10.1212/NXI.0000000000000318 28203615 PMC5292929 · DOI
  11. [11]Gieß RM, Pfuhl C, Behrens JR, et al 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. PLoS One 2017; 12: e0175279. 10.1371/journal.pone.0175279 28388676 PMC5384756 · DOI
  12. [12]von Bismarck O, Dankowski T, Ambrosius B, et al Treatment choices and neuropsychological symptoms of a large cohort of early MS. Neurol Neuroimmunol Neuroinflamm 2018; 5: e446. 10.1212/NXI.0000000000000446 29511705 PMC5833336 · DOI
  13. [13]Niller H-H, Bauer G Epstein-Barr virus: clinical diagnostics. Methods Mol Biol 2017; 1532: 33– 55. 10.1007/978-1-4939-6655-4_2 27873265 · DOI
  14. [14]Compston A, Coles A Multiple sclerosis. The Lancet 2008; 372: 1502– 17. 10.1016/S0140-6736(08)61620-7 18970977 · DOI
  15. [15]Levin LI, Munger KL, O'Reilly EJ, et al Primary infection with the Epstein-Barr virus and risk of multiple sclerosis. Ann Neurol 2010; 67: NA– 30. 10.1002/ana.21978 PMC3089959 20517945 · DOI
  16. [16]Kuhle J, Disanto G, Dobson R, et al Conversion from clinically isolated syndrome to multiple sclerosis: a large multicentre study. Mult Scler 2015; 21: 1013– 24. 10.1177/1352458514568827 25680984 · DOI · Paper page
  17. [17]Pohl D, Krone B, Rostasy K, et al High seroprevalence of Epstein-Barr virus in children with multiple sclerosis. Neurology 2006; 67: 2063– 5. 10.1212/01.wnl.0000247665.94088.8d 17159123 · DOI
  18. [18]Rickinson AB, Kieff E Epstein-Barr virus: Knipe DM, Howley PM, Virology. 4th edn New York: Lippincott Williams and Wilkins, 2001: 2575– 627.
  19. [19]Morris MC, Edmunds WJ, Hesketh LM, et al Sero-Epidemiological patterns of Epstein-Barr and herpes simplex (HSV-1 and HSV-2) viruses in England and Wales. J Med Virol 2002; 67: 522– 7. 10.1002/jmv.10132 12115998 · DOI
  20. [20]Balfour HH, Sifakis F, Sliman JA, et al Age-Specific prevalence of Epstein-Barr virus infection among individuals aged 6-19 years in the United States and factors affecting its acquisition. J Infect Dis 2013; 208: 1286– 93. 10.1093/infdis/jit321 23868878 · DOI · Paper page
  21. [21]Fourcade G, Germi R, Guerber F, et al Evolution of EBV seroprevalence and primary infection age in a French hospital and a City laboratory network, 2000-2016. PLoS One 2017; 12: e0175574. 10.1371/journal.pone.0175574 28414725 PMC5393566 · DOI
  22. [22]De Paschale M, Agrappi C, Manco MT, et al Seroepidemiology of EBV and interpretation of the "isolated VCA IgG" pattern. J Med Virol 2009; 81: 325– 31. 10.1002/jmv.21373 19107979 · DOI
  23. [23]Balfour HH, Odumade OA, Schmeling DO, et al Behavioral, virologic, and immunologic factors associated with acquisition and severity of primary Epstein-Barr virus infection in university students. J Infect Dis 2013; 207: 80– 8. 10.1093/infdis/jis646 23100562 PMC3523797 · DOI
  24. [24]Handel AE, Williamson AJ, Disanto G, et al An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One 2010; 5: e12496. 10.1371/journal.pone.0012496 20824132 PMC2931696 · DOI
  25. [25]Guerrero-Ramos A, Patel M, Kadakia K, et al Performance of the architect EBV antibody panel for determination of Epstein-Barr virus infection stage in immunocompetent adolescents and young adults with clinical suspicion of infectious mononucleosis. Clin Vaccine Immunol 2014; 21: 817– 23. 10.1128/CVI.00754-13 24695777 PMC4054247 · DOI
  26. [26]François C, Segard C, Bouvier M, et al Comparison of Abbott Architect®, Siemens Immulite®, and Diasorin Liaison® for determination of Epstein-Barr virus serological diagnosis. Diagn Microbiol Infect Dis 2018; 90: 96– 101. 10.1016/j.diagmicrobio.2017.10.020 29198371 · DOI

Cited by

Sorted by citations

Authors
Abrahamyan, S., Eberspächer, B., Hoshi, M.-M., Aly, L., Luessi, F., Groppa, S., Klotz, L., Meuth, S. G., Schroeder, C., Grüter, T., Tackenberg, B., Paul, F., Then-Bergh, F., Kümpfel, T., Weber, F., Stangel, M., Bayas, A., Wildemann, B., Heesen, C., Zettl, U., Warnke, C., Antony, G., Hessler, N., Wiendl, H., Bittner, S., Hemmer, B., Gold, R., Salmen, A., & Ruprecht, K.
Affiliations
  • Yerevan State University (AM)
  • Charité – Universitätsmedizin Berlin (DE)
  • TUM Klinikum (DE)
  • Johannes Gutenberg University Mainz (DE)
  • University of Münster (DE)
  • St. Josef-Hospital (DE)
  • Philipps University of Marburg (DE)
  • Institut für Klinische Neuroimmunologie (DE)
  • Sana Kliniken AG (DE)
  • Medizinische Hochschule Hannover (DE)
  • University Hospital Augsburg (DE)
  • Heidelberg University (DE)
  • University Medical Center Hamburg-Eppendorf (DE)
  • University of Rostock (DE)
  • University of Cologne (DE)
  • University Hospital Schleswig-Holstein (DE)
  • University of Bern (CH)
Corresponding author
Ruprecht, Klemens
Venue
Journal of Neurology, Neurosurgery & Psychiatry
Publisher
BMJ
Published
2020-05-05
Volume
91
Issue
7
Pages
681-686
ISSN
  • 0022-3050 (ISSN-L)
  • 1468-330X
OpenAlex
W3021074805
Cited by
119
References
0
Citations by year
2026: 14 · 2025: 19 · 2024: 15 · 2023: 20 · 2022: 22 · 2021: 24 · 2020: 5
FWCI
11.66
Type
journal article
Language
en
Open access
Locations
  • Journal of Neurology Neurosurgery & Psychiatry (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
  • MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (acceptedVersion)
  • BORIS (University Library Bern) (submittedVersion, cc-by-nc)
  • Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by-nc)
  • mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
  • mediaTUM (Technical University of Munich) (submittedVersion)
  • HighWire Press Open Archive (submittedVersion)
  • OPUS (Augsburg University) (submittedVersion, cc-by-nc)
  • Open Access CRIS of the University of Bern
Funders
  • Charité Research Fund
  • German Federal Ministry for Education and Research (01GI0914, 01GI0916, 01GI1601G, 01GI1601B)
  • Stiftung Charité (BIH Clinical Fellow Program)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
  • Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
  • Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
Keywords
Epstein-Barr virus, multiple sclerosis, seroprevalence, viral capsid antigen antibodies, clinically isolated syndrome, relapsing-remitting multiple sclerosis, age-related seropositivity
MeSH terms
Adult, Antibodies, Viral, Herpesvirus 4, Human, Female, Germany, Humans, Male, Middle Aged, Multiple Sclerosis, Registries, Retrospective Studies, Seroepidemiologic Studies

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review