Anti-DNA antibodies tied to multiple sclerosis
By Charles Choi
UPI Science News

LA JOLLA, Calif., Feb. 8 (UPI) -- Scientists recently made two unexpected discoveries relating to multiple sclerosis -- the presence of DNA on nerve cell surfaces and antibodies that targeted DNA. Though the discovery involved only two patients, the findings may open new avenues of research for an often disabling disease whose precise cause remains unknown.

Antibodies -- proteins tailored to react to anything that provokes the immune system -- are an important part of the body's defenses. The general presence of antibodies in the brain and spinal cord is one of the hallmarks of multiple sclerosis, but no one knows for sure what they target there.

Scientists from the Scripps Research Institute in La Jolla, Calif. and the University of Colorado Health Sciences Center in Denver, however, found that in two patients, the antibodies specifically targeted DNA -- any kind of DNA.

"They seem really not to be too fussy about what sort of DNA you present to it," said assistant professor of immunology R. Anthony Williamson, a researcher at Scripps.

Simultaneously, the scientists found DNA on the surfaces of nerve cells grown in petri dishes from multiple sclerosis patients. When the scientists used fluorescent tags to mark the anti-DNA antibodies, they saw that the unusual nerve cells glowed green.

The presence of anti-DNA antibodies and DNA-coated nerve cells suggests multiple sclerosis might be rooted in an immune system response. The immune disorder lupus also has anti-DNA antibodies.

"If you have cells that have DNA on the surface, and these anti-DNA antibodies then coat those cells, there's a potential for triggering other parts of the immune system to attack those particular cells," Williamson said. The team reported their results in this week's Proceedings of the National Academies of Science.

However, Stephen Reingold, vice president of research programs for the National Multiple Sclerosis Society, urged caution because the study examined only two patients.

"There's a need to determine whether or not this is a broader phenomenon in multiple sclerosis," Reingold said. "This is a need the researchers address in their own paper."

Williamson was quick to point out other possibilities as well. "It's a question of what comes first," he said. "It could be that you get cell death and there's a little bit of DNA released and that's when you get the anti-DNA antibodies produced as a consequence. Or you can argue it the other way around, that you get the anti-DNA antibodies produced and that leads to or exacerbates the pre-existing disease."

Other studies have suggested a complex interplay of hereditary and environmental factors may be at work in multiple sclerosis. What is known for sure is that the disease destroys myelin, the insulating sheath that protects the fibers of the nervous system. While multiple sclerosis is not fatal, it is often disabling for the estimated 3 million people who live with it worldwide, with symptoms as mild as numbness or as severe as paralysis and blindness.

The new discovery raises more questions than it answers. For instance, it is unknown as to why the body would have immune system mechanisms tailored especially for DNA.

"It's usually a fairly immunologically inert molecule," Williamson said about DNA. "Which makes sense, because of course we're all full of DNA."

It is also unknown why DNA was present on the surface of the cells the researchers looked at, or what type of DNA it was. Williamson said it was possible that the DNA coating was a quirk of growing the cells in a laboratory setting.

In the meantime, the researchers are trying to get spinal fluid from at least 20 more patients as soon as possible, to see if they too have anti-DNA antibodies.

"We're left with a lot of interesting experiments before we can understand what these results mean," Reingold said.

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