New research doubts links between MS, virus

From Reuters Health:

NEW YORK -- Although studies have found a link between infection with the Epstein-Barr virus and a heightened risk of multiple sclerosis, new findings cast doubt on the theory that the virus helps cause the disease.

In an analysis of spinal fluid and autopsied brain tissue from people with MS, researchers found little evidence of Epstein-Barr genetic material in the samples.

That absence, the researchers say, indicates that the virus is not directly involved in the MS disease process, as a number of other investigators propose.

Multiple sclerosis, or MS, is believed to arise from an abnormal immune system attack on the body's own myelin, a protective sheath surrounding nerve fibers in the brain and spine. This leads to symptoms such as muscle weakness, numbness, vision problems and difficulty with coordination and balance.

Researchers have long suspected that a combination of genetics and an environmental trigger -- such as a virus -- may be to blame for inducing this abnormal immune assault. Studies have particularly focused on Epstein-Barr, an extremely common herpesvirus that causes mononucleosis in some people.

It's believed that nearly everyone -- up to 95 percent of people worldwide -- become infected with Epstein-Barr at some point. After infection, the virus can then take up residence in some of the body's B lymphocytes, a type of immune-system cell, where it dwells in a dormant state.

Some epidemiological studies have found that people with relatively high antibody levels to Epstein-Barr -- possibly indicating a stronger immune response to the infection -- may have a higher risk of MS than people with lower antibody levels.

That, however, is not enough to prove that the virus directly contributes to MS.

For the new study, reported in the journal Neurology, researchers looked for evidence of Epstein-Barr in samples of brain tissue and cerebrospinal fluid from individuals with and without MS.

They found no evidence of Epstein-Barr DNA in B lymphocytes or other cells from MS patients' cerebrospinal fluid. And only a few samples of MS brain lesions harbored genetic material from the virus.

The findings are in line with the majority of published studies looking for evidence of Epstein-Barr in MS brain tissue, according to senior researcher Dr. Donald Gilden, of the University of Colorado School of Medicine in Aurora.

"We feel quite confident that EBV has no role in causing MS," Gilden said in an interview.

He added, however, that he still believes some as-yet-unidentified virus is at work. "I've felt for a long time that a virus is involved in MS," Gilden said. "It's just not Epstein-Barr."

The current findings do conflict, however, with a 2007 study in which researchers found a high rate of Epstein-Barr-infected B lymphocytes in MS brain lesions. Those investigators concluded that "brain infiltration" with those infected cells may be key in the MS process.

For the current study, Gilden and his colleagues included brain-tissue samples from five of the study subjects in the 2007 report (although the specific lesions they examined differed). They failed to find evidence of Epstein-Barr in the samples.

Gilden said the "only explanation" he can think of for the discrepancy is the different techniques the two research teams used to look for Epstein-Barr genetic material. His team used a highly sensitive test called polymerase chain reaction (PCR), which Gilden said is more objective than the technique used in the 2007 study -- known as in situ hybridization.

However, an editorial published with the study asserts that this is far from the end of the story for Epstein-Barr and MS.

Even if the virus is "rare," or only in select types of MS brain lesions, that does not mean Epstein-Barr plays no role in the disease, according to editorialist Dr. Alberto Ascherio of the Harvard School of Public Health in Boston, who has published several studies on the virus and MS.

There are a number of theorized mechanisms by which Epstein-Barr might contribute to MS, write Ascherio and co-author Dr. Amit Bar-Or, of McGill University in Montreal. It's possible, for example, that brain Epstein-Barr-infected B lymphocytes contribute to the disease process earlier on, or transiently.

"These results do not question the importance of (Epstein-Barr) in MS," write Ascherio and Bar-Or, "but rather the predominant anatomic site and disease stage of major (Epstein-Barr) contribution."

But Gilden argued that it is time to look elsewhere for viral culprits in MS. "I would hope that more research in the future will look at other viruses," he said.

If a particular virus were found to contribute to MS, there would be "enormous implications," Gilden said. Such a discovery could, for example, lay the groundwork for a finding a vaccine or drug to help prevent MS.