A study of more than 5,000 patients led by HMS researchers has found a gene variant that protects against multiple sclerosis, an autoimmune disease that damages the nervous system and impairs speech, cognition and motion.
“It’s a small but important step,” said David Hafler, HMS professor of neurology at Brigham and Women’s Hospital and senior author of the study.
Scientists still do not know what causes MS, but they believe there are up to 100 genes making small contributions to its onset. Only eight of those genes have been found so far, said Hafler.
In 2007, his team participated in a major study that identified two new genes tied to MS after screening the genomes of 931 families. The study also hinted at a third gene, called CD58, that seemed to be involved. Now, after analyzing the DNA of 5,326 patients, the Harvard team has confirmed that CD58 has a protective variant against MS; the study was published online Feb. 23 in Proceedings of the National Academy of Sciences. Additional tests showed that variant RNA levels, a telltale sign of the gene’s action, were higher in patients going through a remission than in those experiencing a relapse.
The CD58 variant only accounts for a small protective effect against MS, but it sheds new light on how multiple genes trigger the disease, explained Hafler. “If you have 50 genes on the same pathway, each with a small effect, that small effect becomes a big one.”
Researchers think CD58 is involved in the production of regulatory T cells, a population of immune cells that ease inflammation, one of the major symptoms of MS. The protective allele might alleviate symptoms by enhancing regulatory T cell function, said first author Philip De Jager, HMS assistant professor of neurology at BWH.
The protective variant is more common among East Asians, with around half of the population carrying it, than Europeans, with only 10 percent, said De Jager. The absence of the gene variant could explain a small part of the higher MS rate in Europeans compared with East Asians. “It has a small effect, but it’s one that we can measure,” said De Jager.
De Jager and Hafler said their hunt for new variants has already yielded three additional gene candidates that they will report shortly. “The challenge in front of us is to understand how many small variants lead to the big disease risk,” Hafler said.
Students may contact Philip De Jager at pdejager@rics.bwh.harvard.edu for more information.
Conflict Disclosure: The authors declare no conflicts of interest.
Funding Sources: The National Institutes of Health and the National Multiple Sclerosis Society
