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Researchers find further evidence linking Epstein-Barr virus

Posted: Thu Mar 04, 2010 1:54 pm
by L
http://www.eurekalert.org/pub_releases/ ... 030410.php


Researchers find further evidence linking Epstein-Barr virus and risk of multiple sclerosis
First long-term study among individuals not infected with EBV suggests EBV infection likely to be a cause of MS, not a consequence.

Boston, MA – Researchers from the Harvard School of Public Health, Walter Reed Army Institute of Research, and a team of collaborators have observed for the first time that the risk of multiple sclerosis (MS) increases by many folds following infection with the Epstein-Barr virus (EBV). This finding implicates EBV as a contributory cause to multiple sclerosis. The study appears in an advance online edition of the journal Annals of Neurology and will appear in a later print edition.

Hundred of thousands of individuals not infected with EBV were followed up for several years through repeated blood samples collections. Researchers were then able to determine the time when individuals developed an EBV infection and its relation to MS onset. "The recruitment of individuals before they were infected with EBV and following up with them for several years is the critical methodological aspect that makes this study qualitatively different from all previous work," said Alberto Ascherio, senior author of the study and professor of epidemiology and nutrition at Harvard School of Public Health and professor of medicine at Harvard Medical School.

MS is a chronic degenerative disease of the central nervous system. Women are more likely than men to get the disease and it is the most common neurologically disabling disease in young adults. Although genetic predisposition plays an important role in determining susceptibility, past studies have shown that environmental factors are equally important.

EBV is a herpes virus and one of the most common human viruses worldwide. Infection in early childhood is common and usually asymptomatic. Late age at infection, however, often causes infectious mononucleosis. In the U.S., upwards of 95% of adults are infected with the virus, but free of symptoms. EBV has been associated with some types of cancer and can cause serious complications when the immune system is suppressed, for example, in transplant recipients. There is no effective treatment for EBV.

This is the first study based on the longitudinal follow-up of several thousand individuals who were not infected with EBV at the time of recruitment. The study population was made up of active-duty US Army, Navy, and Marines personnel who have at least one blood sample in the Department of Defense Serum Repository. The electronic databases of the Physical Disability Agencies of the US Army and Navy were then searched for individuals whose records indicated a possible diagnosis of MS reported between 1992 and 2004.

The researchers selected 305 individuals diagnosed with MS and who had blood specimens collected before the date of their diagnosis. Two controls for each case were then selected from the serum database and matched by branch of service, sex, date of blood collection, and age at time of blood collection.

The study found that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.

"The observation that MS occurred only after EBV is a big step forward," said Alberto Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude two non-causal explanations for this finding: that EBV infection is a consequence rather than a cause of MS, and that individuals who are EBV negative could be genetically resistant to MS. Both of these explanations are inconsistent with the present findings," said Ascherio.

"The evidence is now sufficiently compelling to justify the allocation of more resources to the development of interventions targeting EBV infection, or the immune response to EBV infection, as these may contribute to MS prevention," he said

Posted: Fri Mar 05, 2010 3:14 am
by Wonderfulworld
Thanks for posting this study.

I have felt for a long time that a 'perfect storm' situation has to happen to trigger MS
EBV +Low Vitamin-D status+Congenital CCSVI anomolies=MS

Posted: Fri Mar 05, 2010 3:54 pm
by L
Wonderfulworld wrote:I have felt for a long time that a 'perfect storm' situation has to happen to trigger MS
EBV +Low Vitamin-D status+Congenital CCSVI anomolies=MS
I think that you are right, with the addition of really bad luck.

Re: Researchers find further evidence linking Epstein-Barr v

Posted: Sat Mar 06, 2010 9:45 pm
by Apuman
L wrote:Researchers find further evidence linking Epstein-Barr virus and risk of multiple sclerosis
First long-term study among individuals not infected with EBV suggests EBV infection likely to be a cause of MS, not a consequence.
I guess that just helps confirm the common sense deduction that EB somehow plays a causal role. Frankly, I find it hard to conjure how MS could somehow cause a viral infection, but I guess sometimes, to prove that two plus two equals four, one must first prove that two plus two does not equal seven :wink:

Re: Researchers find further evidence linking Epstein-Barr v

Posted: Sun Mar 07, 2010 5:47 am
by L
Apuman wrote:
L wrote:Researchers find further evidence linking Epstein-Barr virus and risk of multiple sclerosis
First long-term study among individuals not infected with EBV suggests EBV infection likely to be a cause of MS, not a consequence.
I guess that just helps confirm the common sense deduction that EB somehow plays a causal role. Frankly, I find it hard to conjure how MS could somehow cause a viral infection, but I guess sometimes, to prove that two plus two equals four, one must first prove that two plus two does not equal seven :wink:
I'd really like to know if people who have had High Dose Cyclophosphamide and relapsed had become re-infected with EBV (presuming that EBV was wiped out along with the person's immune system, the person's B cells.)

Re: Researchers find further evidence linking Epstein-Barr v

Posted: Mon Mar 08, 2010 7:49 pm
by rainer
L wrote:
I'd really like to know if people who have had High Dose Cyclophosphamide and relapsed had become re-infected with EBV (presuming that EBV was wiped out along with the person's immune system, the person's B cells.)
Like seemingly every angle of this disease we have a catch-22: fighting the virus with chemo makes the body immensely more susceptible to contracting the same virus. This is a virus that "in the United States, as many as 95% of adults between 35 and 40 years of age have been infected" with. So reacquiring it almost instantly seems within reason.

Posted: Wed Mar 10, 2010 2:34 pm
by gainsbourg
EBV is part of the herpes family and herpes in all shapes and forms is notorious for how it hides and cloaks itself, and also for how little we known about it.

It was recently discovered that another member of the herpes family - VZV (hepes zoster) has antibodies that increase in the spinal fluid during MS attacks - the worse the attack, the more antibodies. The reason for this is a complete mystery - but since that remarkable finding I've been in no doubt whatsoever that herpes is either a pathogen or a byproduct of MS.

Herpes attacks are notorious for following episodes of stress - just like MS attacks - so there's another possible part of the equation! It could be that rather than MS being an autoimmune illness, herpes is actually the intended target of the body's immune system - it's simply too clever by half at hiding.

Remember, MS is completely unknown in people who have never been infected with the EBV virus.


gainsbourg

Posted: Wed Mar 10, 2010 6:29 pm
by lyndacarol
I have never heard this statement before:
Remember, MS is completely unknown in people who have never been infected with the EBV virus.
Could you supply me with a reference for that information?

Posted: Wed Mar 10, 2010 6:39 pm
by L
lyndacarol wrote:I have never heard this statement before:
Remember, MS is completely unknown in people who have never been infected with the EBV virus.
Could you supply me with a reference for that information?
Here's one study from last year, http://www.springerlink.com/content/qv37535m524u5630/

It says 99%. I remember a study earlier this year said 100% and the study cited at the top of the page implies 100%.

There is a vaccine in trials ( http://en.wikipedia.org/wiki/Epstein-Barr_vaccine ) which I would guess will prove the end of MS.

I would guess taht WonderfulWorld got it about right in the earlier post above, "EBV +Low Vitamin-D status+Congenital CCSVI anomolies=MS" Although I'd add that the vitamin D and the lack of EBV are most likely linked (think of the environment in which MS rates are lowest - sunny countries, and how vitamin D interferes with EBV.

Posted: Thu Mar 11, 2010 2:46 am
by gainsbourg
L and Wonderwall,

L said
There is a vaccine in trials ( http://en.wikipedia.org/wiki/Epstein-Barr_vaccine ) which I would guess will prove the end of MS.
The end of MS! That bold statement really made me stop and think. But they'd also need to vaccinate against VZV, in fact most likely against all forms of herpes.

I particularly enjoy reading people's personal beliefs about the 'MS equation' because there are so many new discoveries about MS floating around, why not attempt to put them all together?

There's been so much about CCSVI lately it's very tempting to link everything MS to vascular problems but we should tread a little cautiously here. The venous reflux thing was a great discovery but it could easily turn out to be a by product of the ongoing inflammatory problem in MS, rather than the cause.

For what it's worth here is (currently) my own attempt at the MS equation:

I believe that a coincidence of viral presence (or attacks) + stressors + deficiencies (like vitamin D) affect nerve metabolism in an unknown way that causes the inflammatory, "autoimmune" process of MS.

The inflammation and metabolic malfunction go on to cause all kinds of side effects such as nerve damage, scarring, iron deposits, vascular problems in the vicinity, fatigue and so on.

In addition, once the vascular problems and iron deposits are formed they act to exasperate and perpetuate the situation. Fixing the veins and removing the iron will help, but not cure the disease.


gainsbourg

Posted: Thu Mar 11, 2010 7:10 am
by patientx
gainsbourg wrote:the venous reflux thing was a great discovery but it could easily turn out to be a by product of the ongoing inflammatory problem in MS, rather than the cause.
I've been thinking the same thing. There's been talk that inflammation can cause stenosis of the veins, so I don't think it's a stretch that whatever inflammatory mechanisms are at work in MS, can also damage the veins. Given that in the preliminary numbers from Jacobs, only about 62% of MS patients had the reflux, I think the idea that the stenosis is a result of the MS gains a little traction.
It was recently discovered that another member of the herpes family - VZV (hepes zoster) has antibodies that increase in the spinal fluid during MS attacks - the worse the attack, the more antibodies.
This is very interesting. Do you have a reference for this?

Posted: Thu Mar 11, 2010 8:19 am
by gainsbourg
Yes, it was in 2007. A research team in Mexico led by Julio Sotelo made a discovery that went largely unnoticed because the abstract was full of jargon.

Almost every adult has had chicken pox. The study found that the chicken pox virus varicella zoster (VZV) - which is a well known form of herpes - was present in the CSF of 95 % of MS patients during relapses, and in 17% during remission. It was not found in the CSF of any of the controls at any time.

Not only that, but as they measured the virus it showed an increasing curve that correlated with the degree off the relapses, until it was 542 times greater than during remission. Not surprisingly, Sotelo seems to think that this virus is "linked to the pathogenisis of MS."

http://cat.inist.fr/?aModele=afficheN&cpsidt=18747883

Herpes attacks tend to occur in episodes - so do MS attacks.

As with many forms of herpes, MS attacks often become less severe over the years (though the damage caused can remain).

Guillain-Barré syndrome (the peripheral nervous system equivalent to MS) is known to be frequently preceded by viral infection.

Stress brings on herpes attacks - stress brings on MS attacks. There's so much correlation here.

By comparison, other theories of MS struggle to explain why the disease so often follows a relapsing/remitting course.

gainsbourg

Posted: Thu Mar 11, 2010 7:52 pm
by L
A VZV vaccine had already been manufactured. I remember that it's only effective for a dozen years or so. Too late to search and see if it's only effective before infection or not, it's way past my bedtime. Night all.

Posted: Fri Mar 12, 2010 2:06 am
by Wonderfulworld
VZV vaccine had already been manufactured. I remember that it's only effective for a dozen years or so. Too late to search and see if it's only effective before infection or not, it's way past my bedtime.
Let us know if you find anything L....even a dozen years might buy us a bit of time!

If anyone else can locate info on a substance that interferes with EBV let us know too.

Background: in 1992 or 1993 I was 2 years post-EBV and still feeling ill, but was working on a job and a colleague bought the Irish Times everyday. I remember reading an article that described a herb that blocked EBV (or Glandular Fever) in the blood. Try as I might, I can't find that article, even though the Irish Times archive is digitised here: http://www.irishtimes.com/search/archive.html odd but then again my research skills are not as sharp as they once were.

Posted: Sat Mar 13, 2010 1:01 pm
by rainer
A lot of EBV research that I have found points to the development of HSP-90 inhibitors mainly in relation to cancer.

http://en.wikipedia.org/wiki/Hsp90

There is a chart nearly at the bottom this page (http://www.gistsupport.org/ask-the-prof ... d-gist.php) with many of these inhibitors currently in trials.

Here is an abstract for one recent study relating HSP-90 inhibitors and MS. http://www.ncbi.nlm.nih.gov/pubmed/19948165