by John C. Martin
Article Date: 08-05-05

Medical experts have theorized in recent years that the cause of multiple sclerosis may be connected to a viral infection in the body.1-3 Now, a new analysis from doctors at Harvard Medical School suggests that high levels of antibodies that target and attack the Epstein-Barr virus may be the culprit in MS.4

Ubiquitous Virus
Epstein-Barr virus (EBV) is one of the most common human viruses, and is responsible for infectious mononucleosis in adolescence or early adulthood in up to 50% of cases. In the United States, an overwhelming 95 percent of people between the ages of 35 and 40 have been infected with the virus at least once in their lives. Infants become susceptible to the virus as soon as maternal antibody protection disappears after birth, and children can also become infected, albeit symptoms are usually hidden or are indistinguishable from those of other common childhood ailments.5

Association Between Age and MS Risk
The latest study suggesting a link between EBV and multiple sclerosis was actually a revised version of an original paper published in the Journal of the American Medical Association two years ago.6 Due to an error in the processing of the study data, the authors retracted the original article and published the revised report in the May 26 issue of the journal.

While the latest study still found a relationship between EBV antibodies and the risk of developing MS, the investigators reported that the association was dependent on a patient's age.

"Anti-EBV antibodies are elevated in individuals with multiple sclerosis, and a premorbid increase has been reported in two studies," wrote Alberto Ascherio, MD, DrPH, of Harvard Medical School, and his colleagues. "But both relied on a single blood sample from each study participant. We, therefore, conducted a larger prospective investigation using serial blood samples collected several years before onset of MS."

The new study prospectively followed 83 patients diagnosed with MS among 3 million military personnel granted temporary or permanent disability due to their illness, and whose blood samples had been stored by the Department of Defense.

Hunting for a Virus
For each of these patients, the researchers identified the earliest available blood sample, plus up to two additional samples collected before MS onset, as well as the first samples collected after MS appeared. The average time between the first blood sample collected and the onset of the disease was four years, the researchers reported.

The researchers then searched for levels of antibodies to EBV in the blood samples collected. They were compared to levels of antibodies against another type of virus. The blood samples from MS patients were also compared with blood samples collected from people without multiple sclerosis.

EBV Link with MS Uncovered
Ascherio and his colleagues found that average antibody levels relative to EBV infection were "significantly higher" among those who later developed MS compared to those without MS, or compared to levels of antibodies against the other virus examined. They also noted that the risk of developing MS increased with increasing levels of these antibodies to EBV. A four-fold increase in the antibody levels was associated with a three-fold increased risk of developing the disease, they wrote.

Next, the researchers wanted to know if levels of EBV antibodies changed with age, given the fact that MS incidence "increases sharply between the ages of 20 and 30 years."

The investigators found that among those who developed MS, antibody levels increased sharply in early adulthood, and then plateaued. In those under age 20, antibody levels were similar to those in patients without MS. But the levels jumped two-to-three-fold by age 25, the researchers reported.

This finding was "striking and unexpected," the research group wrote. "The fact that this increase occurred between the late teens and the mid-to-late 20s, independently from the age of MS onset, supports the hypothesis of an age of vulnerability of the acquisition of MS," the investigators wrote.

While these "modest increases with age" for EBV antibody levels were seen in those patients who later developed MS, the same trend wasn't seen in antibodies against the other virus measured in the study.

In conclusion, the findings suggest that increased levels of antibodies to EBV is not a consequence of MS, but may instead be an early step in the progression of the disease, Ascherio and his team wrote. Further, other studies have linked infection with EBV with an increased risk of lupus,7 "suggesting that EBV may be a risk factor for autoimmune diseases."

1. Haahr S, Sommerlund M, Moller-Larsen A, Mogensen S, Andersen HM. Is multiple sclerosis caused by a dual infection with retrovirus and Epstein-Barr virus? Neuroepidemiology 1992;11(4-6):299-303.
2. Influence of JC virus coding region genotype on risk of multiple sclerosis and progressive multifocal leukoencephalopathy. J Neuroviral 2000 May;6 Suppl 2:S101-8.
3. Kriesel JD, White A, Hayden FG, Spruance SL, Petajan J. Multiple sclerosis attacks are associated with picornavirus infections. Mult Scler 2004 Apr;10(2):145-8.
4. Levin LI, Munger KL Rubertone MV et al. Temporal relationship between elevation of Epstein-Barr virus antibody titers and initial onset of neurological symptoms in multiple sclerosis. JAMA 2005 May 25;293(20):2496-500.
5. Centers for Disease Control and Prevention (CDC). Epstein-Barr Virus and Infectious Mononucleosis. Available at: http://www.cdc.gov/ncidod/diseases/ebv.htm. Accessed July 29, 2005.
6. Levin LI, Munger KL, Rubertone MV et al. Multiple sclerosis and Epstein-Barr virus. JAMA 2003 Mar 26;289(12):1533-6.
7. Parks CG, Cooper GS, Hudson LL et al. Association of Epstein-Barr virus with systemic lupus erythematosus: effect modification by race, age, and cytotoxic lymphocyte-associated antigen 4 genotype. Arthritis Rheum 2005 Apr;52(4):1148-59.

John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.

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