Scientists from Washington University School of Medicine in St. Louis have discovered a possible cause behind a stark gender difference in diagnoses of multiple sclerosis, a new study reports.

Ever since MS research began to proliferate in the last decade or so, researchers have come to find a startling pattern: Women are nearly four times more likely to develop the inflammatory disease than men are. And now, thanks to intense investigation of a specific blood vessel receptor protein and the way the protein interacts with the skull’s blood-brain barrier, an answer may be in sight.

"It was a 'Bingo!' moment — our genetic studies led us right to this receptor," said senior author Dr. Robyn Klein in a statement. When Klein and her colleagues looked at this receptor in mice, they found it indicated clearly how often and in what amount immune cells cross over into the brain. “These cells cause the inflammation that leads to MS."

The protein, known as S1PR2, was found in substantially greater quantities in female brains than in male brains. Females susceptible to MS not only produce more of this receptor protein overall, but they also show even higher levels in the specific brain areas damaged by MS. One of the most popular drugs under investigation right now blocks other proteins in the same protein family, Klein says, but still isn’t designed to block S1PR2. Follow-up research must target this newfound protein.

Even though it affects brain and spinal cord function, MS is formally classified as an inflammatory disease because it has robust ties to the body’s immune system. Popular theories speculate that the myelin-producing cells, which help reduce inflammation, inexplicably begin to fail. This leads to a decay of the insulating covers surrounding nerve cells, and as a result, the nervous system can’t send the proper signals, and characteristic MS symptoms — difficulty walking, dizziness, visual disturbances, and numbness, among others — begin to show. More than two million people worldwide suffer from the disease.

To carry out their study, Klein and her team looked at 20 genes that activate either in the regions susceptible to MS or in places it doesn’t usually harm — investigating these behaviors in both males and females. While 16 of these bore no fruit, among the remaining genes S1PR2 stood out because of its known ability to control the flow of cells and molecules passing through blood vessel walls.

Follow-up tests on human brain tissue after death showed a similar finding: S1PR2 was more common in MS patients than non-MS patients and among women more so than men. The team points out that the highest levels were among two female patients whose MS relapsed and remitted — a term used to describe volatile flare-ups of the disease.

To keep tabs on S1PR2 and to better understand how MS forms, Klein is working on developing a tracer that can follow the receptor protein’s path as it courses through people’s brains. "This is an exciting first step in resolving the mystery of why MS rates are dramatically higher in women,” she said, “and in finding better ways to reduce the incidence of this disorder and control symptoms.”

Source: Cruz-Orengo L, Daniels BP, Dorsey D, et. al. Sexually S1PR2 expression enhances susceptibility to CNS autoimmunity. The Journal of Clinical Investigation. 2014.