A massive, decade-long medical study has removed some lingering doubts that the neurological disease multiple sclerosis (MS) is linked to a common viral infection. For years, research findings have pointed toward the connection, but whether the infection is a cause, a result, or unrelated to MS has remained an open question.
Now, in a large-scale investigation into that question, researchers have found a statistical smoking gun linking risk of the disease to the body’s long-lasting immune response to Epstein-Barr virus.
Epstein-Barr, a herpes virus, infects more than 9 in 10 people worldwide. Fortunately, most tots who catch it develop just a mild flu, and people infected later in life usually come down with nothing worse than mononucleosis (SN: 10/10/98, p. 229).
In contrast, the crippling autoimmune disease MS occurs in about 1 in 1,000 people in the United States. The disease unfolds as a person’s immune cells attack a protein called myelin. Sheaths of myelin normally wrap around and protect parts of nerve cells. The autoimmune attack causes the nerve cells to malfunction and can produce coordination and speech problems. Genetics plays a role, but precisely what triggers the onset of MS remains unknown.
To investigate the virus’ purported link to MS, Alberto Ascherio of the Harvard School of Public Health in Boston and his team took blood samples from more than 62,000 women. The researchers tested the blood for antibodies that bind specifically to the Epstein-Barr virus. Many of the participants harbored such antibodies in their blood, indicating that they had previously been infected.
Eighteen of the women were diagnosed with MS during the 10-year study. The researchers compared the prediagnosis concentrations of antibodies in those patients with the concentrations in volunteers who didn’t develop MS. Relative to the women without MS, those who developed symptoms had, on average, four times the blood concentration of one type of Epstein-Barr antibody. The 126 women with MS when the study began also had elevated Epstein-Barr antibodies, Ascherio’s team reports in the Dec. 26, 2001 Journal of the American Medical Association.
The study is “an important addition to the growing body of literature suggesting a link between [Epstein-Barr virus] and MS,” says Robert D. Siegel, an immunologist at Stanford University.
This research has a design advantage over previous studies, says David A. Hafler of Harvard Medical School in Boston. Most participants were tested before they exhibited MS symptoms, thereby reducing the likelihood that the disease elevates viral-antibody concentrations.
Hafler deems the finding an “important step forward” in unearthing the roots of MS, but he cautions that it “doesn’t directly answer the question of whether [Epstein-Barr virus] causes the disease.”
Still, genetic factors that underlie the immune system’s misdirected activity in MS could independently explain the differences in antibody concentrations that the Harvard researchers observed, says H. Michael Dosch of the Hospital for Sick Children in Toronto, who remains unconvinced of the virus-MS connection. “The smoking gun could have been a whole lot smokier,” says Dosch.