"Researchers Find Further Evidence Linking Epstein-Barr Virus, Risk of MS"

Dolphin

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[I've appended the abstract but think the lay version is useful here also. Given the EBV involvement, I thought some might find it of interest]

DGNews

Researchers Find Further Evidence Linking Epstein-Barr Virus, Risk of MS

BOSTON -- March 4, 2010 -- Researchers 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 senior author Alberto Ascherio, MD, Harvard School of Public Health, and Harvard Medical School, Boston, Massachusetts.

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 1 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 Dr. Ascherio. "Until now we knew that virtually all MS patients are infected with EBV, but we could not exclude 2 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."

"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.

SOURCE: Harvard School of Public Health
===========================

http://www3.interscience.wiley.com/journal/123246497/abstract

Annals of Neurology
Volume 9999 Issue 999A, Page NA
Published Online: 20 Jan 2010

Copyright C 2010 American Neurological Association

Brief Communication

Primary infection with the epstein-barr virus and risk of multiple sclerosis


Lynn I. Levin, PhD, MPH 1, Kassandra L. Munger, ScD 2, Eilis J O'Reilly, ScD
2 3, Kerstin I Falk, PhD 4, Alberto Ascherio, MD, DrPH 2 3 5 *

1Department of Epidemiology, Division of Preventive Medicine, Walter Reed Army Institute of Research, Silver Spring, MD 20910-7500 2Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA 3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA 4Department of Virology, Swedish Institute for Infectious Disease Control, and MTC, Karolinska Institute, Solna, Sweden 5Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and Harvard Medical School

email: Alberto Ascherio (aascheri@hsph.harvard.edu)

*Correspondence to Alberto Ascherio, Professor of Epidemiology and Nutrition, Harvard School of Public Health, 665 Huntington Ave, Building II, Room 335, Boston, MA 02115

Abstract

To determine whether multiple sclerosis (MS) risk increases following primary infection with the Epstein-Barr virus (EBV), we conducted a nested case-control study including 305 individuals who developed MS and 610 matched controls selected among the over 8 million active-duty military personnel with serum stored in the Department of Defense Serum Repository.

Time of EBV infection was determined by measuring antibody titers in serial serum samples collected before MS onset among cases, and on matched dates among controls. Ten (3.3%) cases and 32 (5.2%) controls were initially EBV negative. All of the 10 EBV-negative cases became EBV positive before MS onset; in contrast, only 35.7 % (10) of the 28 controls with follow-up samples seroconverted (exact p value = 0.0008). We conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection. Ann Neurol 2010.

----------------------------------------------------------------------------
Received: 14 October 2009; Revised: 8 December 2009; Accepted: 8 January 2010
 

Hope123

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This is interesting tomk. What I like about it is that it traced healthy people from the time before they had EBV.

The methods used are similar to a studies on lupus from the University of Oklahoma, which also took blood from military recruit repositiories, and was able to show that the first autoimmune antibodies developed in lupus cross-react with antibodies developed to EBV. This implied that EBV could be the trigger starting lupus, which then propogates and blossoms unfortunately. Fascinating stuff. I suspect the MS researchers might look start to look at MS antibodies and see whether they cross-react with EBV.
 

Dr. Yes

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Wow. That's all I have to say for now. I wonder if these researchers will look at HHV-6 as well, in that or other neurological diseases. I know the HHV-6 Foundation has suggested links with that virus as well; will have to check.
 
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MS Risk Linked to Smoking and EB Viral Antibodies

By Michael Smith, North American Correspondent, MedPage Today
Published: April 07, 2010
Reviewed by Zalman S. Agus, MD; Emeritus Professor
University of Pennsylvania School of Medicine and
Dorothy Caputo, MA, RN, BC-ADM, CDE, Nurse Planner

[if: and now this news on top of the stud tomk posted]

* Explain to interested patients that this study found a link between smoking, antibody response to Epstein-Barr virus, and the risk of multiple sclerosis.

Smoking appears to increase the chances of developing multiple sclerosis in people who already have one of the established risk factors for the disease, researchers said.

In patients with high antibody levels against Epstein-Barr virus -- known to enhance the risk of MS -- smoking nearly doubled the chances of developing the illness, according to Claire Simon, ScD, of Harvard School of Public Health, and colleagues.

On the other hand, smoking did not modify the risk associated with another factor, the HLA-DRB1*1501 immune system haplotype in Caucasians, Simon and colleagues wrote online in Neurology.


The finding comes from an analysis of three case-control studies of MS -- the American Nurses' Health Study/Nurses' Health Study II, the Tasmanian MS Study in Australia, and a Swedish MS study.

"The consistency of an association between MS, smoking, and the body's immune response to the Epstein-Barr virus based on these three distinct, geographically diverse studies suggests this finding is not due to chance," Simon said in a prepared statement.

The link "may provide clues as to why certain individuals develop MS while others do not," she said.

The link between a powerful antibody response to Epstein-Barr virus and MS has been known for some time. (See Epstein-Barr Linked to Multiple Sclerosis)

A smoking history and the immune system variant have also been linked to the disease. Simon and colleagues recently reported that the immune system variant and response to Epstein-Barr are independent risk factors, but the role of smoking and possible three-way interactions was not known.

To help clarify the issue, they looked at the three studies, which involved a total of 442 people with MS and 865 healthy controls.

Participants were stratified according to Epstein-Barr antibody levels; for those below the median, there was no association between past or current smoking and the risk of MS.

However, for those above the median, the researchers found, having smoked at any time was associated with a 70% increase in risk. (The odds ratio was 1.7, with a 95% confidence interval from 1.1 to 2.6, which was significant at P=0.004.)

And the effect of high Epstein-Barr antibody levels was stronger among past or current smokers, they wrote.

Among those with high antibody levels, the odds ratio for MS among those who had ever smoked was 3.9, with a 95% confidence interval from 2.7 to 5.7, compared with 1.8 among those who had never smoked (with a 95% confidence interval from 1.4 to 2.3.) The interaction was significant at P=0.001.

On the other hand, Simon and colleagues said, there was no interaction between smoking and the HLA-DRB1*1501 immune system haplotype or between high Epstein-Barr antibody levels and the immune system variant.

The authors noted that the study is limited by different exposure assessments across studies. They also said it was not possible to account for changes over time in smoking behavior, and few participants had Epstein-Barr antibody levels tested before the onset of MS symptoms.

Nevertheless, they wrote, the finding seems unlikely to be a chance effect and more study is needed to tease out the mechanism involved.

The study was supported by the NIH, the National Health and Research Council of Australia, the Australian Rotary Health Research Fund, and MS Australia.

Simon is supported by NIH Kirschstein-NRSA.

Primary source: Neurology
Source reference:
Simon KC, et al "Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk" Neurology 2010; 74: 1-1.
 

oerganix

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yikes! what's the chance of having CFS with elevated EBV and then ALSO getting MS????? ~Fern
Unfortunately, probably elevated as well. Genetics might also have something to do with whether your CFS progresses to MS. And some PWCs have been "wrongly" diagnosed with MS.

I have elevated titers to EBV. I have a cousin with MS, another with lupus and they both have autistic kids. I trace all of this suseptibility through our maternal grandmother, bless her sweet soul.

I just wish the CDC had started a longitudinal study like this on CFS 10 or 20 years ago, as they should have done, instead of pissing away the money and our lives with psuedo-research about "emotional neglect" (cold mother) and/or childhood sexual abuse (neglectful mother). We really need to get those woman-hating old men out of CDC and replace them with women and men who care about everybody.
 
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Pathway in MS May Drive Treatment Outcome

Pathway in MS May Drive Treatment Outcome
Posted by SR in News, tags: MS

[if: I thought the emerging proof for 2 distinct versions of MS was fascinating. Treatment would depend on which sub-group was in]

Although interferon-β (IFN-β) is used to reduce the number and severity of relapses in patients with relapsing remitting multiple sclerosis (RRMS), a frustration for both patients and physicians is that the treatment is more effective in some patients than others. Studies by researchers at Stanford University and colleagues have now suggested that there may be two distinct versions of multiple sclerosis and that the effectiveness of β-interferon may depend on the type of disease that the patient has.

The team found that superficially similar experimental autoimmune encephalitis (EAE), an animal model of multiple sclerosis, can be induced either by T helper type 1 (TH1) cells or by TH17 cells. IFN-β was effective in treating TH1-induced EAE but exacerbated disease caused by TH17 cells. In TH1-induced EAE, treatment was accompanied by increased interleukin-10 (IL-10) production whereas in TH17-induced EAE, IL-10 levels were unaffected by treatment, although IL-17 levels were reduced. Both induction of IL-10 production and suppression of IL-17 levels were dependent on IFN-γ; in the absence of IFN-γ signalling, IFN-β did not reduce the symptoms of EAE.

The team then measured IL-17 levels in blood samples from 26 RRMS patients taken before and about 2 years after starting treatment with IFN-β. When treatment responses were matched to IL-17 levels a clear pattern emerged: patients with a good response had very low levels of the IL-17 family member, IL-17F, whereas those who responded poorly about 30% of the patients had high levels of IL-17F. Although the team caution that the results need to be confirmed in larger groups of patients, the study has the potential to transform treatment for MS by stratifying patients into likely IFN-β responders and non-responders.

Eventually, a simple blood test could improve the response rate to IFN-β and spare non-responders from the known flu-like side effects of a treatment that could even worsen their disease.

The study is published in the journal Nature Medicine.
 

bel canto

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Since MS patients have many, many crossover symptoms with cfs patients, I thought I'd put another reference on here.

The MS community has been in turmoil since a recent theory has been supported by continuing research. It's thought by some that most MS patients have a venous malformation in major veins that drain from the brain and spinal cord, resulting in reflux that crosses the blood-brain barrier and activates a destructive immune response. The condition is known as CCSVI - chronic cerebral venous insufficiency, and some patients are reporting dramatic results with angiography-type surgeries. There are many major questions out there, including how this theory fits in with the known association of some of the viral infections that are also common with cfids and fm, as well as ms.

Of interest is also the fact that rrm patients seems to have different patterns of venous insufficiency than pp do. Stanford is involved with this, also.
 

August59

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Unfortunately, probably elevated as well. Genetics might also have something to do with whether your CFS progresses to MS. And some PWCs have been "wrongly" diagnosed with MS.

I have elevated titers to EBV. I have a cousin with MS, another with lupus and they both have autistic kids. I trace all of this suseptibility through our maternal grandmother, bless her sweet soul.

I just wish the CDC had started a longitudinal study like this on CFS 10 or 20 years ago, as they should have done, instead of pissing away the money and our lives with psuedo-research about "emotional neglect" (cold mother) and/or childhood sexual abuse (neglectful mother). We really need to get those woman-hating old men out of CDC and replace them with women and men who care about everybody.

To think where we might be if the appropriate amount of funding would have been given.
 
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Gerwyn

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Wow. That's all I have to say for now. I wonder if these researchers will look at HHV-6 as well, in that or other neurological diseases. I know the HHV-6 Foundation has suggested links with that virus as well; will have to check.
definately not a herv
 

starryeyes

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We conclude that MS risk is extremely low among individuals not infected with EBV, but it increases sharply in the same individuals following EBV infection.
This is not too surprising to me. I've always felt that my illness has a lot in common with MS ever since I came down with EBV at the age of 20. I wonder how CFS and FM are related.

Hope, it's interesting that EBV is implicated in starting Lupus in people as well. Lupus is another illness that's very similar to MS, CFS and FM.