Very interesting.
Well ‘caused by’ only in the same way it’s caused by breathing. I think over 90% of the population get this virus. But it’s good to learn about mechanisms.
I need to dig up the paper, but my understanding is that most people get EBV (from another paper EBV is highly prevalent since it affects more than 90% of individuals worldwide. Oh yeah what @Fifth_Fret said.)
I guess we should think about it the other way: almost nobody that is EVB free develops MS. So it’s a contributing factor or the start of a some interaction that requires other (likely genetic) components to occur.
So, this just kicks the can down the road a bit to: why are people who develop MS different from people who don’t conditional on everyone having EVB.
I wonder if you add in other viruses that are less common if you get similar effects. Did our one non-EVB patient have some similar infection (coronavirus, everybody panic?) that pushed them along this path?
The article kind of glazed over that part about the one non-EVB patient. I don’t really understand why that doesn’t disprove this theory.
One final question from Ascherio’s data concerns the lone EBV-negative MS patient in the study. The paper’s discussion section identifies infection in between sampling or failure to seroconvert as potential explanations, but another reason, Ascherio suggests, may be due to the limitations of diagnosis.
“Before the polio vaccine, say 99% of poliomyelitis cases were caused by the polio virus, but, unless you define the disease based on the infectious agent, for any disease, there will be occasional cases that are not caused by that that agent,” says Ascherio. For example, acute flaccid paralysis – which was virtually eradicated after the success of the polio vaccination program, still is seen in rare cases. “There is no reason,” says Ascherio, “that MS should be an exception, because, even if MS is a complication of EBV infection, when you describe the disease clinically and radiologically, there will always be an occasional case that is due to something else.”
I’m really hoping that between this and Long Covid we’ll see some real breakthroughs in understanding the mechanisms underlying virus-triggered auto-immune diseases. Maybe down the road we’ll get relief for lupus, CFS and others.
It’s an association, it’s statistically significant (haven’t read the paper!) and biology is messy. You can’t 100% say that in one case out of 700 people the antibody test didn’t fail, for example. That’s why you generally do these studies with large numbers of people, to overcome that statistical variation in your signal.
There’s always noise and uncaptured variation, that doesn’t bother me a bit. There could be more “fun” to be had trying to figure out (as I said above) if there was another similar viral infection that they didn’t test for in that person.
EBV is a gateway illness; while many bodies may try it once or twice and move along, others can’t get the same feeling after a while and need a stronger illness. That’s how they come across MS. So really, just say no to EBV.
(j/k if not otherwise obvious)
@Fifth_Fret Hey look mom there’s mechanism!
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.