Epstein-Barr virus protein can “switch on” risk genes for autoimmune diseases

Indigophoton

Indigophoton

Senior Member (Voting Rights)
Infection with Epstein-Barr virus (EBV), the cause of infectious mononucleosis, has been associated with subsequent development of systemic lupus erythematosus and other chronic autoimmune illnesses, but the mechanisms behind this association have been unclear. Now, a novel computational method shows that a viral protein found in EBV-infected human cells may activate genes associated with increased risk for autoimmunity. Scientists supported by the National Institute of Allergy and Infectious Diseases report their findings today in Nature Genetics.
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The researchers looked at genetic and protein information from both healthy people and those with autoimmune conditions, using a newly developed technique.
In the current study, the researchers found that EBNA2 and its related transcription factors activate some of the human genes associated with the risk for lupus and several other autoimmune diseases, including multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease.
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“Because EBV is most often encountered in early childhood, avoiding infection is practically impossible,” said Daniel Rotrosen, M.D., director of the Division of Allergy, Immunology and Transplantation at NIAID. “However, now that we understand how EBV infection may contribute to autoimmune diseases in some people, researchers may be able to develop therapies that interrupt or reverse this process.”
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https://www.nih.gov/news-events/new...ein-can-switch-risk-genes-autoimmune-diseases

The paper, https://www.nature.com/articles/s41588-018-0102-3
 
I don't get this. We all have EBV so how can having had it be a risk factor? My mum looked at this decades ago and some people with autoimmune disease are EB negative so you do not even need it. EBV switches on B cells like billy-oh but we have known that for ages. B cell switching on goes wrong in autoimmunity so by definition EB will turn on things related to autoimmunity. I just don't get what the evidence for any causal role is (or for anything new for that matter).
 
Jonathan Edwards said:
We all have EBV so how can having had it be a risk factor?
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I do not believe that EBV is a risk factor for everyone who encounters it. Some people get severe mono, they recover, and it never affects them again. But in others, it can lead to ME/CFS, to MS, to autoimmunity, and even to cancer. It is a risk factor in those who are susceptible to it (even if we do not yet know why).

Jonathan Edwards said:
EBV switches on B cells like billy-oh but we have known that for ages.
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I have no idea what "billy-oh" is but if you are agreeing that EBV can switch on B cells (autoimmunity) in certain individuals, than I am confused why you are saying that it cannot?

Jonathan Edwards said:
B cell switching on goes wrong in autoimmunity so by definition EB will turn on things related to autoimmunity. I just don't get what the evidence for any causal role is (or for anything new for that matter).
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I bolded what you said b/c I think you actually agree with my doctors re: EBV turning on autoimmunity (in some individuals, of course not in all). I don't think it is actually something new, maybe just more doctors or studies are starting to recognize it or become more interested in it.
 
Gingergrrl said:
Both of my doctors believe there is a very good chance that EBV (which I somehow managed to avoid until age 41 when I got mono) is responsible for my shift into severe autoimmunity today.
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I got mono at 39 in 1999 and have never recovered.

I wonder that perhaps it wasn't that we didn't get mono until decades after most but rather that our immune systems for whatever reason could no longer keep the EBV in check/latent state?
 
Jonathan Edwards said:
SOrry, @Gingergrrl, but you have completely missed my point. There is no evidence for EBV causing autoimmunity as far as I know. It switches on pathways that also happen to be switched on in autoimmunity but that means something completely different.
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I guess we agree to disagree as usual :banghead:;). My doctors who know my entire case are convinced it was viral (EBV + others) that shifted into autoimmunity several years post-Mono. I would have to ask them re: the specific evidence but they state it as a if it were a given (but I guess this is still debated by doctors).

janice said:
I got mono at 39 in 1999 and have never recovered. I wonder that perhaps it wasn't that we didn't get mono until decades after most but rather that our immune systems for whatever reason could no longer keep the EBV in check/latent state?
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I my case, it was not a re-activation of EBV when I got Mono at age 41 (in 2012), it was actually my first exposure believe it or not. I had been tested for EBV during my neurotoxic reaction to Levaquin (in 2010) as part of trying to rule out everything else. I was completely negative on every single EBV test (IgM, IgG, EA, EBNA, VCA, etc). Then in 2012 when I got mono, I was still negative on IgG but positive on IgM.

I recovered from Mono in approx 6-8 wks but got sick again in Jan 2013 but did not recover and within 2 wks, I developed POTS. When we checked (a few months later) I was highly IgM+ and EA+ again for EBV and stayed this way for several years until we believe I shifted into autoimmunity.
 
Gingergrrl said:
This video was posted on the other board and it explains how the EBV virus leads to autoimmune diseases. It explains it better than I ever could!

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:thumbup: Thanks for posting
That is very interesting and very exciting. Whooopeee.

One of his free access papers from 2013 is also very interesting :
Rubicz R, Yolken R, Drigalenko E, Carless MA, Dyer TD, et al. (2013) A Genome-Wide Integrative Genomic Study Localizes Genetic Factors Influencing Antibodies against Epstein-Barr Virus Nuclear Antigen 1 (EBNA-1). PLoS Genet 9(1): e1003147. doi:10.1371/journal.pgen.1003147

Enjoy.:hug:
 
Gingergrrl said:
This video was posted on the other board and it explains how the EBV virus leads to autoimmune diseases. It explains it better than I ever could!
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Sadly it does not explain anything, @Gingergrrl. The fact that a protein binds to molecule that are involved in autoimmunity does not in any sense indicate that the protein causes these diseases. It is a pity that scientists hype their work so much these days. He says that they have found something amazing but then when it is explained it tells us nothing. People have been working on EBA and lupus for forty years. My mum worked on it in the 1980s. Nothing has changed as far as I can see.
 
Jonathan Edwards said:
Sadly it does not explain anything, @Gingergrrl
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It explains it to me and there is a really interesting discussion about it on the other board. I wish there could be one here too vs. all the research being immediately dismissed. I thought maybe it was just the studies from Dr. Sheibenbogen & Cell Trend & OMF but this is from Cincinnati Children’s.

Jonathan Edwards said:
It is a pity that scientists hype their work so much these days.
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It didn’t seem like hype to me vs. a legitimate group of researchers sharing their findings. This is to get funding and collaborators at other institutes to join them. Why would that be a “pity”? It could lead to a new discovery!

Jonathan Edwards said:
People have been working on EBA and lupus for forty years.
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Is EBA the same as EBV?
 
EBA should have been EBNA, sorry. EBNA is an EBV antigen that has been around for yonks - my mum used to study it with patrick Venables.

The video is hype to me. The claim is that something revolutionary has been found but there is nothing new I can see here in terms of autoimmunity. Thirty years ago scientists did not talk like this and didn't need to. You do not need to talk like that to get funding. Colleagues who know anything about the subject will not be impressed. They would be much more impressed if the interpretation was sober and measured.

I am sorry we do not have jolly discussions about how wonderful research is over here but the whole point of having a forum focusing on science is to make as accurate an analysis as we can of the significance of things. The other forum always worried me because people seemed to be rushing off to try treatments that were clearly based on pseudoscience and no good evidence. I would be equally worried if people were discussing how wonderful 50% interest payday loans were and everyone was signing up for them.
 
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Jonathan Edwards said:
EBA should have been EBNA, sorry. EBNA is an EBV antigen that has been around for yonks - my mum used to study it with patrick Venables.
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Sorry, I did not realize you meant EBNA (and that is one of the tests I have been positive on since having Mono). I just Googled yonks (and still don't know what billy means!) and I sometimes feel I do not know enough British terminology to follow some of these discussions (but that is my fault, and not a criticism)!

Jonathan Edwards said:
The video is hype to me. The claim is that something revolutionary has been found but there is nothing new I can see here in terms of autoimmunity. Thirty years ago scientists did not talk like this and didn't need to. You do not need to talk like that to get funding. Colleagues who know anything about the subject will not be impressed. They would be much more impressed if the interpretation was sober and measured.
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For me it was a short four minute video that was explaining to colleagues and lay-people what they found and what they hope to research further. For me it doesn't matter if they are excited about their findings (vs. sobered and measured which is your preference). I just want to hear the findings and if more doctors & researchers understand that there is a connection between EBV and autoimmunity, this is thrilling to me and backs up what both of my doctors believe occurred in my case. And this is a major hospital, not some random sketchy clinic.

Jonathan Edwards said:
I am sorry we do not have jolly discussions about how wonderful research is over here but the whole point of having a forum focusing on science is to make as accurate an analysis as we can of the significance of things.
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I am not looking for jolly discussions, I just wish we were allowed to discuss it at all without being told it is BS within the first few posts which tends to shut down discussions for those of us who do not think it is BS.

Jonathan Edwards said:
The other forum always worried me because people seemed to be rushing off to try treatments that were clearly based on pseudoscience and no good evidence. I would be equally worried if people were discussing how wonderful 50% interest payday loans were and everyone was signing up for them.
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I do not consider research on EBV and autoimmunity to be pseudoscience (and have no idea what a 50% payday loan is). Maybe I am just more suited for the other board as much as I really do like this one, too.
 
Gingergrrl said:
For me it doesn't matter if they are excited about their findings (vs. sobered and measured
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@Gingergrrl, for background info, in general, it's not how scientists feel about their results that is the issue, but how cautiously or incautiously they interpret them. Typically scientists are very careful to ascribe neither more nor less than the results support to what they find.

It seems that in at least some fields these days there is a trend towards hyperbole, perhaps because of career pressure.

Hype may not be apparent to those insufficiently familiar with a particular field, but for anyone who works in or near that field, who is any good, it is, actually, an immediate first indicator of a less good scientist/paper.

Edit: typo
 
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