ECTRIMS2021. EBV infection before damage

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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.

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MouseDoctor

20 comments

  • Is there also evidence on EBV-reactivations being more frequent with MS-patients than in the general population? Or put differently: does having MS also affect EBV-reactivations?
    If so, is it possible that at least some of the famous MS-fatigue can be caused by EBV-reactivations?

  • I was never the same after I had infectious mononucleosis as a 17 year old at the beginning of
    my senior year in high school.
    I had a severe case and missed six weeks of school. I also wasn’t allowed to take part in physical ed because of enlarged spleen.
    It was not until I was 56 years old that I was finally diagnosed with MS after years of neurological symptoms. The only time I felt really well was when I was 22 and pregnant with my only child. I am now 66 and on Ocrevus treatment since early 2018.

  • Very interesting thank you for sharing. I wonder if neuro filament light chains go back to normal levels for those on antiretrovirals which some target EBV.

  • But why 58,1% and not 100% after EBV if EBV is the cause? And 95% of the population has had EBV, and is high sNfL levels only related to MS?

    • Correct me if I am wrong but as I understand the 58% part, it says that people who later on developed MS, had a mean increase in sNFL of 58.1%, not that only 58.1% had an increase of sNFL. Is that correct?

  • Crazy. Let’s hope a treatment targeting EBV is found soon.

    Maybe an EBV treatment for people with already MS won’t be to much effect

  • I think prof G covered this study in a video someone shared here. Since we are discussing the US army, I think there was a study about the increase of MS in Kuwait after operation desert storm. Sounds very similar to a country prof G talked about in his video about the increase in MS after WW2. Not sure what country it was but I think it was Faroe Islands.

  • I would so like the same amount of wonderful research funding that has been applied to the SARS-CoV-2 virus to also be applied to EBV. What a difference that would make.

    • “I would so like the same amount of wonderful research funding that has been applied to the SARS-CoV-2 virus to also be applied to EBV.”

      What funding..? It only took hours to design the vaccines.

      We Had the Vaccine the Whole Time
      https://nymag.com/intelligencer/2020/12/moderna-covid-19-vaccine-design.html

      “Moderna’s mRNA-1273, which reported a 94.5 percent efficacy rate on November 16, had been designed by January 13. This was just two days after the genetic sequence had been made public in an act of scientific and humanitarian generosity that resulted in China’s Yong-Zhen Zhang’s being temporarily forced out of his lab. In Massachusetts, the Moderna vaccine design took all of one weekend.”

      “China began administering a vaccine to its military in June. Russia approved its version in August. And while most American scientists worried about the speed of those rollouts, and the risks they implied, our approach to the pandemic here raises questions, too, about the strange, complicated, often contradictory ways we approach matters of risk and uncertainty during a pandemic — and how, perhaps, we might think about doing things differently next time. That a vaccine was available for the entire brutal duration may be, to future generations trying to draw lessons from our death and suffering, the most tragic, and ironic, feature of this plague.”

    • “Serum Nfl is a good proxy for Csf Nfl?”

      Why not.?..Csf drains into the blood..

      “The arachnoid emerges into the dural sinuses as the arachnoid granulations, where the CSF is filtered back into the blood for drainage from the nervous system.”

    • I know a few patients who’s neurologists do monthly serum Nfl’s for them. The idea is to prevent relapses, guess what, it doesn’t work.

  • I had glandular fever aged 18. CIS ? aged 40. Other risk factors like my birth mother probably had MS but died the same year so I couldn’t ask he about her experiences. Maybe a red herring but EBV must be in the frame.

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