Epstein-Barr Virus Found to Trigger Multiple Sclerosis (ScientificAmerican)

[BrightCandle]

https://www.scientificamerican.com/article/epstein-barr-virus-found-to-trigger-multiple-sclerosis/

They used two decades of blood samples from more than 10 million young adults on active duty in the U.S. military (the samples were taken for routine HIV testing). About 5 percent of those individuals (several hundred thousand people) were negative for Epstein-Barr when they started military service, and 955 eventually developed MS. The researchers were able to compare the outcomes of those who were subsequently infected and those who were not.

These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS,

The bottom line is almost: if you’re not infected with EBV, you don’t get MS. It’s rare to get such black-and-white results.

After infection, Epstein-Barr lives on in some B cells of the immune system and the antibodies developed to fight it remain in the blood.

Ascherio and his colleagues also measured antibodies against cytomegalovirus, another herpesvirus, and found no difference in levels in those who developed MS and those who did not

I think this is a very interesting finding, EBV is clearly not mostly benign anymore and ME/CFS has some interesting similarities to MS and doctors often struggle to rule it out early on in the disease.

 

[Pyrrhus]

Here's the original Science article, which was just published:

Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis (Bjornevik et al., 2022)
https://www.science.org/doi/10.1126/science.abj8222

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.

 

[Pyrrhus]

Possibly related discussion:

How Viruses Cause Autoimmunity
https://forums.phoenixrising.me/threads/how-viruses-cause-autoimmunity.86598/

In some cases, autoimmunity seems to develop only after a long period of chronic inflammation, similar to what has been observed in multiple sclerosis. (Where studies suggest that the disease process in multiple sclerosis begins many years before any autoimmunity might be detected.)

 

[Pyrrhus]

Lead author Alberto Ascherio had previously published a paper on the epidemiology of ME, which unfortunately relied on the outdated Fukuda diagnostic criteria:

Incidence of myalgic encephalomyelitis/chronic fatigue syndrome in a large prospective cohort of U.S. nurses (Palacios et al., 2017)
https://forums.phoenixrising.me/thr...s-in-a-large-prospective-cohort-of-u-s.51591/

Methods: We sent an email questionnaire to participants in the Nurses’ Health Study II (NHS II), a large prospective cohort of female nurses. Forty-two thousand three hundred and ninety-four women completed the questionnaire, which included the 1994 Centers for Disease Control and Prevention (CDC) criteria for ME/CFS.

Results: One-hundred and two women (240 per 100,000 surveyed) developed an illness that met criteria for ME/CFS between 1989 and 2009. The onset of ME/CFS was gradual in 40.6%, sudden (following flu-like illness or other precipitating events) in 18.8%, followed emotional or physical trauma in 32.3%, and was uncertain in the rest. Under-diagnosis was common: only 15 (15%) of the women who met criteria for ME/CFS reported having been diagnosed. Over-diagnosis also was common: four times as many subjects had been diagnosed with ME/CFS by community doctors as actually met criteria. The distribution of symptoms was not different in comparing cases with a sudden onset to those with a gradual onset.

 

[Husband of]

I also came across this article suggesting ebv involvement in seven automiimune diseases, unfortunately it didn’t mention cfs but still interesting.

https://www.sciencedaily.com/releases/2018/04/180416121606.htm

 

[WinterWren]

https://www.hsph.harvard.edu/news/p...s-may-be-leading-cause-of-multiple-sclerosis/

Now, if they can just figure out what’s going on with EBV… hurry research!

 

[lenora]

I wish we could find one common link between most viruses and other illnesses that may be offshoots of them.

It's becoming more and more apparent that one virus leads to another to another. Not even the ones first suspected. Why are we having this genetic damage....and what causes it? Yours, Lenora.

 

[Murph]

The "cause" of MS has been discovered but not the mechanism. The good news is there will probably be a ton of research now into post-EBV disease mechanisms. Is the virus hiding in the nerves? Is its genome inserted in our genomes? lurking in mitochondria? Or are the viral particles gone while their legacy lives on, thanks to some other mechanism?

 

[Learner1]

EBV has been linked to autoimmunity for several years:

https://pubmed.ncbi.nlm.nih.gov/26424654/

https://www.medscape.com/viewarticle/780170

https://www.futuremedicine.com/doi/full/10.2217/fvl.12.1

https://www.nih.gov/news-events/nih-research-matters/epstein-barr-virus-autoimmune-diseases

It also has been linked to several cancers. This explains how it can trigger cancer development:

https://www.livescience.com/epstein-barr-virus-mono-cancer-link.html

 

[lenora]

Hi @Learner 1.......I think we have a long way to go before the entire story of not only EBV but all viruses (at least major ones) can cause lasting damage to some individuals.

Lots of questions still out there. Yours, Lenora.

 

[wabi-sabi]

I was so excited to see this. It makes me think research is really picking up. But raises and interesting question: in some people EBV triggers MS and in some it triggers ME/CFS. I really wonder why. In some alternate reality I have MS. Hmmm....

 

[lenora]

HI @ Wabi-Sabi.....A good neurologist would be able to distinguish between the two illnesses. You probably go for a yearly check-up anyway, so you could bring the question up at that time.

I would imagine that even a rheumatologist would also be able to do the same. An MRI will show any lesions you may have. Bear in mind that most people recover from EBS without other problems.....I hope you'll be among them. Yours, Lenora.

 

[YippeeKi YOW !!]

Epstein-Barr Virus Causes Multiple Sclerosis: Study
https://www.the-scientist.com/news-...P_Q&utm_content=200877502&utm_source=hs_email

“ Experts say new research provides strong evidence that a common herpesvirus can trigger the chronic inflammatory disease.”

It’s not a large step from there to accepting that the same virus can trigger ME/CFS. Which begs the question, “Should we be grateful that we weren’t triggered into MS, a much more difficult, devastating illness with far more profound and potentially lasting QOL issues.?”

There’s always something to be grateful for, but sometimes you really have to dig for it.

Read on ….

 

[wabi-sabi]

A good neurologist would be able to distinguish between the two illnesses

If only I could get one of those who didn't assume that all my problems were depression when the test results came back negative.

What I meant was, since I have ME/CFS from mono (I think), in another life or alternate reality where I have a slightly different genetic make up I got MS from the same infection, where in this life I got ME/CFS. I just love scifi!

 

[Violeta]

Herpes virus seems to be very comfortable in the brain, for some reason.

 

[Pyrrhus]

It is important to note that EBV is not the only virus that has been linked to multiple sclerosis (MS)...

Detection of coronavirus RNA and antigen in multiple sclerosis brain (Murray et al., 1992)
https://dx.doi.org/10.1002/ana.410310511

We report the in situ hybridization detection of coronavirus RNA in 12 of 22 MS brain samples using cloned coronavirus cDNA probes. In addition, tissue was screened for coronavirus antigen by immunohistochemical methods; antigen was detected in two patients with rapidly progressive MS. Significant amounts of coronavirus antigen and RNA were observed in active demyelinating plaques from these two patients. These findings show that coronaviruses can infect the human central nervous system and raise the possibility that these viruses may contribute to the pathogenesis of MS in some patients.

 

[Pyrrhus]

Related discussion:

Clonally Expanded B Cells in Multiple Sclerosis Bind EBV EBNA1 and GlialCAM (Lanz et al., 2022)
https://forums.phoenixrising.me/thr...rosis-bind-ebv-ebna1-and-glialcam-2022.86795/
Main point:

• It presents an interesting hypothesis regarding molecular mimicry:

Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBNA1 and the CNS protein GlialCAM.

Abstract
Multiple sclerosis (MS) is a heterogenous autoimmune disease in which autoreactive lymphocytes attack the myelin sheath of the central nervous system (CNS).

B lymphocytes in the cerebrospinal fluid (CSF) of MS patients contribute to inflammation and secrete oligoclonal immunoglobulins1,2. Epstein-Barr virus (EBV) infection has been linked to MS epidemiologically, but its pathological role remains unclear3.

Here we demonstrate high-affinity molecular mimicry between the EBV transcription factor EBNA1 and the CNS protein GlialCAM, and provide structural and in-vivo functional evidence for its relevance.

A cross-reactive CSF-derived antibody was initially identified by single-cell sequencing of the paired-chain B cell repertoire of MS blood and CSF, followed by protein microarray-based testing of recombinantly expressed CSF-derived antibodies against MS-associated viruses.

Sequence analysis, affinity measurements, and the crystal structure of the EBNA1-peptide epitope in complex with the autoreactive Fab fragment allowed for tracking the development of the naïve EBNA1-restricted antibody to a mature EBNA1/GlialCAM cross-reactive antibody.

Molecular mimicry is facilitated by a post-translational modification of GlialCAM. EBNA1 immunization exacerbates the mouse model of MS and anti-EBNA1/GlialCAM antibodies are prevalent in MS patients.

Our results provide a mechanistic link for the association between MS and EBV, and could guide the development of novel MS therapies.

 

[seamyb]

ME/CFS is a messed up innate immune system - oxidative stress and microglial cell hyperactivity.

MS is a messed up adaptive immune system - generation of antibodies which target host cells (particularly nerve cells).

I think these oversimplified statements together are profound. EBV can trigger a messed up immune system but chooses a flavour depending on its mood.

 

[Pyrrhus]

Related discussions:

Epstein-Barr virus genetic variants are associated with multiple sclerosis. (Mechelli et al, 2015)
https://forums.phoenixrising.me/thr...are-associated-with-multiple-sclerosis.36790/

Molecular mimicry between Anoctamin 2 and Epstein-Barr virus nuclear antigen 1 associates with multiple sclerosis risk (Tengvall et al., 2019)
https://forums.phoenixrising.me/thr...ssociates-with-multiple-sclerosis-risk.78421/

MS reversed by transplanted immune cells that fight Epstein-Barr virus (New Scientist, 2022)
https://forums.phoenixrising.me/thr...ne-cells-that-fight-epstein-barr-virus.87463/

 

[Pyrrhus]

DePaul University Professor of Psychology Leonard Jason, PhD and Solve M.E. President and CEO Oved Amitay recently co-authored a response to a Nature article linking Epstein-Barr virus (EBV) and multiple sclerosis (MS), and the possibility that EBV vaccines and antivirals could prevent MS. Jason and Amitay note the connection between ME/CFS and EBV call for similar research into preventive vaccines for ME/CFS.
https://solvecfs.org/solve-m-e-ceo-...nard-jason-write-letter-to-the-editor-nature/

Excerpt:

Mullard’s recent article highlights the evidence suggesting Epstein-Barr virus (EBV) as a causative factor for multiple sclerosis (MS) and the potential to prevent this devastating disease. Other potentially preventable post-viral diseases should receive attention, specifically, myalgic encephalomyelitis (ME/CFS)- a debilitating disease also associated with EBV. Nearly all cases of Infectious Mononucleosis (IM) are caused by EBV and 9-13% of individuals do not fully recover from IM and meet criteria for ME/CFS 6 months following onset.