Epstein-Barr Virus May Play Role in Multiple Sclerosis Development

For decades, researchers have suspected that people infected with a very common virus, Epstein-Barr, may be more likely to develop multiple sclerosis, a neurological disease that affects 1 million people in the United States. Now, a team of researchers has reported on what some say is the most compelling evidence to date of a strong link between the two diseases.

The virus infects nearly everyone in their teens or young adults, and only a few develop multiple sclerosis. The researchers also note that it’s not the only known risk factor for people who develop the disease. But they say their data suggests it’s the clearest of them all. While it remains to be seen whether the finding will lead to treatments or treatments for multiple sclerosis, the study may further stimulate research into treatments and vaccines for the condition.

In their study, published Thursday in the journal Science, the group examined data from 10 million people on active duty in the US armed forces over two decades. The strength of their study lies in their ability to follow people for years and ask whether Epstein-Barr infection predates multiple sclerosis, said lead researcher Dr. Alberto Acchirio, an epidemiologist at Harvard T.H. Chan School of Public Health.

Among the service members in the study, 801 had multiple sclerosis, a disabling disease that occurs when the immune system attacks the fatty insulation that protects nerves in the brain and spinal cord. Most of those who develop the disease are diagnosed between the ages of 20 and 50. The disease is rare, although an individual’s chance of developing multiple sclerosis is half one percent.

Meanwhile, the virus in question, Epstein-Barr, is common, infecting nearly everyone at some point. Although few are aware that they are infected, some develop mononucleosis. The virus remains in the body for life.

Since very few people infected with the virus develop multiple sclerosis, it cannot be the only cause of the disease. Other risk factors, including some, such as low levels of vitamin D and smoking, previously seen by the Harvard group, were identified using the same data set. There are genetic factors, too — 900 abnormal genes have been identified in patients with MS, said Dr. Anthony J. Rieder, a multiple sclerosis expert at the University of Chicago, who was not involved in the new study. Gender plays a role, too; Most of the patients are women.

But, as Dr. Ashrio said, no risk factor is as prominent as an Epstein-Barr infection.

To ask how much the virus increased risk, the investigators studied the small percentage of people who did not contract the virus early in their careers but did afterwards. They detect infection by having antibodies to the virus.

Among patients with MS, 32 out of 33 were infected with the Epstein-Barr virus before developing MS

As a control group in their study, the scientists tracked 90 individuals who did not initially develop Epstein-Barr and who also did not develop multiple sclerosis. Of those, 51 subsequently developed Epstein-Barr.

This means that infection with the Epstein-Barr virus increased the risk of developing multiple sclerosis more than 30 times, Dr. Ashrio said.

But Dr. Rieder cautioned that it can be difficult to derive cause and effect from an epidemiological study. People with multiple sclerosis have an overactive immune system, which causes them to develop high levels of antibodies to a viral infection. Multiple sclerosis may arise not from the virus but from the body’s response to it.

“Multiple sclerosis patients have fewer viral infections than usual,” he said, because their immune systems are so active that they are effectively fighting off viruses. People with MS often say, “I never catch a cold.” When I hear that, my ears pulse.”

Dr. Rieder noted that medications currently used to treat multiple sclerosis suppress the immune system. He added that so far, antiviral drugs have not helped patients with multiple sclerosis.

The Harvard group tried to control for the possibility that the immune system response, not the virus itself, would increase the risk of developing multiple sclerosis in people with Epstein-Barr. They asked if antibodies to another common virus, CMV, were also associated with a higher risk of developing multiple sclerosis. they were not.

But Dr. Rieder said CMV appears to protect against multiple sclerosis for unknown reasons. So the fact that people with it do not have a higher risk of developing multiple sclerosis may not be surprising.

Others said the study was compelling evidence of cause and effect.

“The way it was done is very compelling,” said Dr. Michael David Kornberg, a multiple sclerosis specialist at Johns Hopkins. “It’s really the most compelling data we have on causal association.”

This leaves the question of what to do now.

Dr. Bruce Curry, a multiple sclerosis researcher at the University of California, San Francisco, notes that it can be difficult to treat multiple sclerosis by stalking Epstein-Barr because the actual virus can be difficult to find in patients. Although multiple sclerosis is a disease of the brain and spinal cord, he was unable to find the virus in the patients’ spinal fluid.

But patients appear to be harboring cells in their brains that produce EBV antibodies. Dr. Cree is investigating whether he can cure MS patients by removing those cells infected with the Epstein-Barr virus.

An experimental anti-mRNA vaccine against Epstein-Barr was one approach designed to prevent the virus from affecting the brain, said Dr. Lawrence Steinman, a multiple sclerosis researcher at Stanford, who wrote a perspective accompanying the Harvard group’s paper.

Now the question, he said, is, “Can we get rid of multiple sclerosis?”

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