Our immune cells normally pounce on intruding bacteria and viruses. But in multiple sclerosis (MS), immune cells target the nervous system instead. Now, researchers may have pinpointed a long-sought molecule called a self-antigen that provokes these attacks, pointing a way toward potential new treatments.
“The work is monumental, and it’s tantalizing,” says neuroimmunologist Hartmut Wekerle of the Max Planck Institute of Neurobiology in Munich, Germany, who wasn’t connected to the research.
Researchers have long suspected that a self-antigen—a normal molecule in the body that the immune system mistakenly treats as a threat—can trigger MS. The prime suspects have been proteins in myelin, the nerve insulation that erodes in patients with the disease. But after years of searching, scientists haven’t been able to pinpoint the molecule.
To uncover other candidates, immunologists Roland Martin and Mireia Sospedra of University Hospital of Zurich in Switzerland and their colleagues analyzed immune cells known as T cells that came from a patient who died from MS. T cells normally switch on when they encounter protein fragments containing just a few amino acids that belong to an invading microbe, but they also turn on in people who have MS.
The researchers wanted to determine which protein shards stimulated the patients’ T cells, so they tested 200 fragment mixtures, each containing 300 billion varieties. The two fragments with the strongest effect turned out to be part of a human enzyme called guanosine diphosphate-L-fucose synthase, which helps cells remodel sugars that are involved in everything from laying down memories to determining our blood type. T cells from 12 of 31 patients who had who either had been diagnosed with MS or had shown early symptoms of the disease also reacted to the enzyme, the researchers report online today in Science Translational Medicine. What’s more, T cells from four of the eight patients tested responded to a bacterial version of the enzyme—lending credence to the recently proposed idea that intestinal bacteria may help spark the disease.