The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis
Abstract
Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system of unknown etiology. We tested the hypothesis that MS is caused by Epstein-Barr virus (EBV) in a cohort comprising more than 10 million young adults on active duty in the US military, 955 of whom were diagnosed with MS during their period of service. Risk of MS increased 32-fold after infection with EBV but was not increased after infection with other viruses, including the similarly transmitted cytomegalovirus. Serum levels of neurofilament light chain, a biomarker of neuroaxonal degeneration, increased only after EBV seroconversion. These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS.
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“This phenomenon is particularly relevant considering recent data demonstrating that EBV infection is a necessary risk factor for MS and that cross-reactive immune responses between EBV antigens and CNS proteins may contribute to disease initiation [211, 212].”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [212]
In the citing paper
“For example, type 1 diabetes mellitus was linked to enterovirus infections185 and multiple sclerosis to Epstein–Barr virus (EBV) infections186.”
From COVID-19 and cellular senescence (2023) · cites this paper as [186]
Citations
Cites
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Neurofilaments as biomarkers in neurological disorders
Khalil, M., Teunissen, C. E., Otto, M., Piehl, F., Sormani, M. P., Gattringer, T., Barro, C., Kappos, L., Comabella, M., Fazekas, F., et al. (2018) · Nature Reviews Neurology · doi:10.1038/s41582-018-0058-z · Cited by 1,988
Negative Controls: A Tool for Detecting Confounding and Bias in Observational Studies
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Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis
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Epstein-Barr virus: exploiting the immune system
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Sun, L., Su, Y., Jiao, A., Wang, X., & Zhang, B. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01471-y · Cited by 1,153
Clonally expanded B cells in multiple sclerosis bind EBV EBNA1 and GlialCAM
Lanz, T. V., Brewer, R. C., Ho, P. P., Moon, J.-S., Jude, K. M., Fernandez, D., Fernandes, R. A., Gomez, A. M., Nadj, G.-S., Bartley, C. M., et al. (2022) · Nature · doi:10.1038/s41586-022-04432-7 · Cited by 908
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Klein, J., Wood, J., Jaycox, J. R., Dhodapkar, R. M., Lu, P., Gehlhausen, J. R., Tabachnikova, A., Greene, K., TABACOF, L. R., Malik, A. A., et al. (2023) · Nature · doi:10.1038/s41586-023-06651-y · Cited by 852
Unexplained post-acute infection syndromes
Choutka, J., Jansari, V., Hornig, M., & Iwasaki, A. (2022) · Nature Medicine · doi:10.1038/s41591-022-01810-6 · Cited by 604
Jakimovski, D., Bittner, S., Zivadinov, R., Morrow, S. A., Benedict, R. H. B., Zipp, F., & Weinstock‐Guttman, B. (2023) · The Lancet · doi:10.1016/s0140-6736(23)01473-3 · Cited by 695
Metadata
- Authors
- Bjornevik, K., Cortese, M., Healy, B. C., Kuhle, J., Mina, M. J., Leng, Y., Elledge, S. J., Niebuhr, D. W., Scher, A. I., Munger, K. L., & Ascherio, A.
- Affiliations
- Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
- Harvard University (US)
- Brigham and Women's Hospital (US)
- Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel, University of Basel, Basel, Switzerland.
- Uniformed Services University of the Health Sciences (US)
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
- Corresponding author
- Cortese, Marianna
- Munger, Kassandra L.
- Ascherio, Alberto
- ORCID
- Venue
- Science
- Published
- 2022-01-21
- Volume
- 375
- Issue
- 6578
- Pages
- 296-301
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W4205972999
- Cited by
- 2,049
- References
- 51
- Citations by year
- 2026: 354 · 2025: 412 · 2024: 461 · 2023: 432 · 2022: 388
- FWCI
- 289.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS042194, R01NS046635, R01NS103891)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Health Sciences › Medicine › Oncology › Viral-associated cancers and disorders
- Health Sciences › Medicine › Epidemiology › Cytomegalovirus and herpesvirus research
- Keywords
- multiple sclerosis, Epstein-Barr virus, viral etiology, neurofilament light chain, neuroaxonal degeneration, cytomegalovirus, demyelinating disease, military personnel
- MeSH terms
- Antibodies, Viral, Cytomegalovirus, Herpesvirus 4, Human, Female, Humans, Longitudinal Studies, Male, Military Personnel, Multiple Sclerosis, Risk Factors, Cohort Studies, Biomarkers, Prevalence, Neurofilament Proteins, Age of Onset, Epstein-Barr Virus Infections, Young Adult
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