The US Military has an amazing set-up and have samples and monitoring of their soldiers. They have shown in the past that EBV infection is always evident before MS develops. This study shows that neurofilaments as a marker of nerve damage occurs after EBV infection so more evidence for it being in the causal pathway
K. Bjornevik1, M. Cortese1, B.C. Healy2,3,4, D. Leppert5, D.W. Niebuhr6, A.I. Scher6, J. Kuhle5, K.L. Munger1, A. Ascherio1,7,8
1Harvard T.H. Chan School of Public Health, Department of Nutrition, Boston, United States, 2Brigham and Women’s Hospital, Partners Multiple Sclerosis Center, Boston, United States, 3Harvard Medical School, Department of Neurology, Boston, United States, 4Massachusetts General Hospital, Biostatistics Center, Boston, United States, 5University of Basel, Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Basel, Switzerland, 6Uniformed Services University of the Health Sciences, Department of Preventive Medicine and Biostatistics, Bethesda, United States, 7Harvard T.H. Chan School of Public Health, Epidemiology, Boston, United States, 8Brigham and Women’s Hospital and Harvard Medical School, Channing Division of Network Medicine, Boston, United States
Introduction: Epstein-Barr virus (EBV) infection consistently precedes the clinical onset of multiple sclerosis (MS), but it remains uncertain whether it precedes the onset of asymptomatic or unrecognized demyelinating attacks. If EBV, as it has been proposed, is a cause of MS, EBV infection should precede the first signs of demyelination.
Objectives: To assess whether concentrations of serum neurofilament light chain (sNfL), a biomarker of neuroaxonal damage, are elevated before, around, and after the time of primary EBV infection in individuals who later developed MS.
Methods: We conducted a nested case-control study among active-duty US military personnel who have serum samples stored in the Department of Defense Serum Repository. We measured antibodies against EBV antigens in up to three serum samples from 490 MS cases and 960 controls matched by age, sex, race/ethnicity, and dates of sample collection, and identified 25 MS cases and 79 controls who were EBV-negative in the first sample. In these individuals, we measured serum neurofilament light chain (sNfL) concentrations using an ultrasensitive single-molecule array (Simoa) assay and compared log-transformed levels in cases and controls using linear regression and linear mixed-effects regression.
Results: There were no significant differences in sNfL levels in cases and controls in serum samples collected before and around the time of primary EBV infection. In serum samples collected after EBV infection, sNfLs levels were higher in MS cases than in controls (p = 0.026). In MS cases, there was a 58.1% (95% CI: 21.3-106.8, p = 0.006) within-person increase in sNfL levels in the samples collected after EBV infection compared to the samples collected before EBV infection, while there was no significant increase in the samples collected around the time of EBV infection (-2.1%, 95% CI: -24.9-27.5, p = 0.89).
Conclusions: There were no signs of neuroaxonal degeneration before primary EBV infection in individuals who later developed MS. This suggests that EBV infection precedes the onset of the pathological process leading to MS, which is consistent with it being a cause and not a consequence of MS.