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.

Neurological Benefits, Clinical Challenges, and Neuropathologic Promise of Medical Marijuana: A Systematic Review of Cannabinoid Effects in Multiple Sclerosis and Experimental Models of Demyelination

“…Other risk factors for MS include smoking, alcohol consumption, obesity, low dietary intake of vitamin D, lower sun exposure, latitude farther away from equator, and certain chronic viral infections [39]. Longitudinal analysis using data from US military recruits over a period of 20 years has revealed that Epstein-Barr virus (EBV) increased the risk of subsequent MS by 32-fold [41]. MS patients have significantly higher serum anti-EBV nuclear antigen-1 (EBNA-1) titers as compared to healthy controls, and the higher EBV responses correlate with more extensive lesion and gray matter tissue destruction as measured by magnetization transfer imaging in RRMS patients [42].…”

A Final Frontier in Environment-Genome Interactions? Integrated, Multi-Omic Approaches to Predictions of Non-Communicable Disease Risk

“…The International Multiple Sclerosis Genetics Consortium, and others, have published numerous GWAS to identify genetic factors that contribute to MS [e.g., ( Consortium et al, 2007 ; International Multiple Sclerosis Genetics Consortium, 2019 ; Mo et al, 2019 )], however, there are also multiple known environmental risk factors for MS development, most prominently, lack of vitamin D exposure, smoking, and exposure to Epstein-Barr virus (EBV) ( O’Gorman et al, 2012 ). For example, a recent longitudinal study in military veterans demonstrated a strong link between EBV and MS ( Bjornevik et al, 2022 ). Despite these known associations, and the complex interplay between genetics and the environment, most studies of MS focus only on GWAS, or are conducted at the candidate-gene level, for example, correlations between promoter methylation and gene expression levels ( Hosseini et al, 2020 ).…”

“…Based on evidence gathered from research into other NCDs, namely, that an integrated, multi-omic approach is valuable and insightful, together with the paucity of such approaches being applied to MS, highlights how much MS research will benefit from the integration of multiple layers of genomic data, particularly in light of the strong and well-identified environmental factors [e.g., ( Bjornevik et al, 2022 )]; this approach will allow us to interrogate the impact of the environment and the genome on MS progression, providing novel insights into the biological basis of disease development and progression.…”

High prevalence of intrathecal IgA synthesis in multiple sclerosis patients

“…IgA is a main response to viruses 9 – 13 , and they have been related to MS in the last years 14 – 16 . Moreover, IgA-positive plasma cells present in the central nervous system (CNS) tissues of MS patients were claimed to be the main source of IgA deposits along axons detected in the lesions, which in turn, were related with axonal damage 17 .…”