5 April, 2003
Scott Gottlieb, New York
Evidence is mounting that infection with the Epstein-Barr virus (EBV), which can cause mononucleosis, may also increase the risk of developing multiple sclerosis later in life.
Previous studies have established a link between the viral illness and multiple sclerosis (JAMA 2001;286:3083-8) [Full Text], and now in a new study, investigators have discovered that people with the highest levels of antibodies directed against EBV possibly indicating a history of severe infection were more than 30 times as likely to develop multiple sclerosis later in life than those with the fewest antibodies (JAMA 2003;289:1533-6) [Full Text].
EBV is an extremely common type of herpes virus, with more than 90% of the population in countries such as the United States and the United Kingdom estimated to have been infected at some point. The vast majority of people carry anti-EBV antibodies, and only a small number develop multiple sclerosis.
Previous research has shown that people with multiple sclerosis tend to carry higher levels of anti-EBV antibodies (including IgA against EBV VCA (viral capsid antigen) and IgG against VCA, nuclear antigens). Whether the increase in antibodies precedes multiple sclerosis, however, has remained unclear.
In the current study, researchers led by Dr Alberto Ascherio of the Harvard School of Public Health examined blood samples from 83 people who later developed multiple sclerosis and compared them with blood samples from 166 people without the condition. The study used a nested case-control design and was conducted in more than three million US military personnel; blood samples were collected between 1988 and 2000 and stored in the Department of Defense Serum Repository.
Cases were considered to be individuals who were granted temporary or permanent disability because of multiple sclerosis. For each case (n=83), two controls matched by age, sex, race/ethnicity, and dates of blood sample collection were selected.
All the people who developed multiple sclerosis carried anti-EBV antibodies in their blood, as did 96% of those without multiple sclerosis. However, antibody levels at the start of the study were consistently higher among those who later developed the disease.
On average, these people developed symptoms of multiple sclerosis four years after their blood samples were takensuggesting there's a long lag time between infection with EBV and onset of multiple sclerosis. The strongest predictors of multiple sclerosis were serum levels of IgG antibodies against VCA or against the EBV nuclear antigen (EBNA) complex.
The risk of multiple sclerosis increased with these antibody titres; relative risk in people in the highest category of VCA (2560) compared with those in the lowest (160) was 19.7 (95% confidence interval 2.2 to 174; P for trend 0.004).
No one is sure why the immune systems of people with multiple sclerosis decide to launch an attack on their own tissue, Dr Ascherio noted. Scientists have suspected that a combination of factorsincluding genetics and environmental triggers such as virusesmay set off the aberrant attack.
The researchers reasoned that, as people with high levels of anti-EBV antibodies seem to be at higher risk, some of the immune cells that become programmed to attack the virus may "cross react" and begin to attack myelin as well.
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© 2003 BMJ Publishing Group Ltd