Multiple sclerosis is triggered by the mononucleosis virus – they proved it.

Scientific American hails a breakthrough in fighting MS with the definitive discovery that the Epstein-Barr virus, which causes mononucleosis and which 95% of American adults carry, is indeed the trigger for developing multiple sclerosis:

esearchers at the Harvard T. H. Chan School of Public Health and Harvard Medical School turned to what they call “an experiment of nature.” They used two decades of blood samples from more than 10 million young adults on active duty in the U.S. military (the samples were taken for routine HIV testing). About 5 percent of those individuals (several hundred thousand people) were negative for Epstein-Barr when they started military service, and 955 eventually developed MS. The researchers were able to compare the outcomes of those who were subsequently infected and those who were not. The results, published on September 13 in Science, show that the risk of multiple sclerosis increased 32-fold after infection with Epstein-Barr but not after infection with other viruses. “These findings cannot be explained by any known risk factor for MS and suggest EBV as the leading cause of MS,” the researchers wrote.

In an accompanying commentary, immunologists William H. Robinson and Lawrence Steinman, both at Stanford University, wrote, “These findings provide compelling data that implicate EBV as the trigger for the development of MS.” Epidemiologist Alberto Ascherio, senior author of the new study, says, “The bottom line is almost: if you’re not infected with EBV, you don’t get MS. It’s rare to get such black-and-white results.”

In the new study, which is a much larger expansion of a 2010 investigation, the researchers analyzed up to three blood samples for each individual with MS: the first taken when most of the military personnel were under the age of 20, the last taken years later, before the onset of the disease, and one in between. The team was looking for seroconversion, or the appearance of antibodies in the blood as evidence of infection. Each person with MS was also matched with two randomly selected controls without MS, who were of the same age, sex, race or ethnicity, and branch of the military. Out of the 955 cases of MS, they were able to assemble appropriate samples for 801 individuals with the disease and 1,566 controls. Thirty-five of the people who developed MS and 107 controls tested negative for EBV initially. Only one of the 801 people with MS had not been infected with Epstein-Barr before the disease’s onset. The risk of developing MS was 32 times greater for those who seroconverted by the third sample, compared with those who did not. As for the one case of MS in someone who remained negative for Epstein-Barr, it is possible that person was infected after the sample was taken, but it is also true that, in diseases that are clinically defined by their symptoms, such as MS, it is highly unlikely that 100 percent of cases derive from the same cause, even if most do, Ascherio says.

But to be sure Epstein-Barr was the culprit, Ascherio and his colleagues also measured antibodies against cytomegalovirus, another herpesvirus, and found no difference in levels in those who developed MS and those who did not. Using a subset of 30 MS cases and 30 controls, they conducted a scan to detect antibody responses to most of the viruses that infect humans. Again, there was no difference. And to rule out the possibility that infection with Epstein-Barr preceded MS and not the other way around, the team also measured levels of a protein that is elevated in serum when neurons are injured or die and that therefore serves as a marker of the beginning of the pathological process before clinical symptoms appear. The protein levels only rose after Epstein-Barr infection.

Even if Epstein-Barr is the triggering event for MS, infection alone is insufficient for an actual diagnosis. Epstein-Barr, it appears, has to combine with a genetic predisposition and possibly environmental factors, such as smoking and vitamin D deficiency, to increase risk.