By Isabella Colonna
For March we have selected Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science. 2022 Jan 21;375(6578):296-301. doi: 10.1126/science.abj8222. Epub 2022 Jan 13. PMID: 35025605.
Our research paper of the month for March is a cohort study exploring the risk of developing multiple sclerosis (MS) after infection with Epstein-Barr virus (EBV). A cohort of more 10 million active-duty US military personnel between 1993 and 2013 was screened for EBV using the residual serum from the tests used for HIV screening and archived in the Department of Defense Serum Repository.
This cohort included 801 individuals who developed MS during the follow-up and 1566 age and sex-matched controls with three serum samples collected before MS onset and suitable to assess EBV infection. At baseline, the serum of 35 MS cases and 107 controls was EBV-negative. During the follow-up, the seroconversion was significantly higher in the individuals who later developed MS (97%) than in controls (57%). The hazard ratio for MS comparing EBV seroconversion versus persistent EBV seronegativity was 32.4 (95% CI: 4.3 to 245.3, p<0.001).
In order to evaluate if this risk factor for MS could be explained by environmental or individual characteristics which may predispose to both infection and MS, the authors assessed the presence of infection with cytomegalovirus (CMV) in the same serum samples. CMV was chosen as control because it is a herpesvirus, like EBV, which is transmitted by saliva and displays socioeconomic and ethnic disparities in age at infection in the US population similar to those of EBV. They found that individuals who later developed MS and controls presented a similar rate of seroconversion for CMV.
Furthermore, the authors aimed to investigate the temporal relation between EBV infection and MS by assessing the serum concentration of neurofilament light chain (sNFL), which is a marker of axonal degeneration. It was shown that sNfL levels in subjects who were not infected with EBV at baseline and later developed MS were similar to those of controls, but they increased after EBV infection. This finding indicates that EBV infection precedes not only the onset of MS symptoms but also the first neurodegenerative changes of the disease.
In conclusion, this study suggests that EBV infection might be the leading cause of MS and, therefore, the development of an effective vaccine for EBV could potentially prevent MS.