Researchers say a molecule that helps blood clot may also play a role in multiple sclerosis relapses. The new study may help answer the question of why remissions happen, as well as find early disease markers. The research also shows a new way to study MS in mice that is closer to the human form of the disease.

Most people with MS have recurring episodes of disability, followed by remissions when their symptoms lessen or disappear. Why these relapses and remissions happen is a great mystery. Researchers know that the immune system causes damage to the nerves. In MS patients, a particular type of immune cell – CD8+ cells, a part of the immune system that normally kills cells that are cancerous or infected – are the ones doing the damage.

Although scientists have been able to develop drugs to help fight MS using a mouse version of MS, these experimental mice develop a slightly different immune system response than what happens in MS in humans. Different cells do the damage in MS mice: CD4+ cells. The mice have CD8+ cells, but those CD8+ cells are generally quiescent. This has been a big stumbling block to understanding how the immune system develops in MS.

However, a team of researchers from UConn Health, the University of Illinois at Chicago, and the Gladstone Institutes have figured out how CD8+ cells are activated in MS mice, and the result seems very close to what happens in humans. The new findings hinge on how cells talk to each other. Cells will often secrete little bubbles containing proteins and genetic signals. These bubbles are called extracellular vesicles, or EVs. EVs are made by most cells in the body, and float in the blood stream like a message in a bottle.

The team injected EVs from normal, healthy mice into mice that had that experimental MS-like disease. When they did this, the mice acquired a relapsing-remitting disease and active CD8+ cells, like human MS patients. The researchers examined the EVs in mice and patients with MS and found they contained fibrinogen. Fibrinogen normally helps blood clot and seal up wounds. But in these MS mice, the EVs with fibrinogen seemed to activate the CD8+ immune cells. When they injected the MS mice with EVs that did not have fibrinogen, then they could not cause the relapsing-remitting illness.

Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, the researchers would like to understand how the fibrinogen stimulates the CD8+ cells that cause the relapsing and remitting disease activity. They would also like to test whether fibrinogen and related proteins found in the EVs also play a role in humans with MS, and test if these molecular signals in EVs might be early warnings of relapses or disease progression.

The findings were published in the journal PNAS.