Gut immune cells may help send MS into remission

November 20, 2020

An international research team led by UCSF scientists has shown, for the first time, that gut immune cells travel to the brain during multiple sclerosis (MS) flare-ups in patients. These gut cells seem to be playing a protective role, helping drive MS symptoms back into remission.

Scientists know that in MS, other types of immune cells go haywire and attack myelin, crucial insulation material that helps nerve cells communicate with one another quickly and reliably. The resulting damage leads to periodic MS attacks that can leave patients struggling with vision loss, memory problems, pain and other symptoms. These "relapse" symptoms often subside on their own after days or weeks, but medical experts still don't have a good understanding of what flips the switch from flare-up to remission and back again.

The new findings, published November 20, 2020 in Science Immunology, suggest that an unexpected new player might help bring flare-ups under control: immune cells from the gut that express a type of antibody called IgA. In the gut, these cells serve as a critical first line of defense against foreign invaders and, scientists think, help keep the teeming bacteria of our gut microbiome from growing out of control. Recently, a UCSF-led international research team made the surprising discovery that, in animal models of MS, these
"It was a very new idea," said Sergio Baranzini, PhD, a professor of neurology and member of the UCSF Weill Institute for Neurosciences, lead author on the new study. "Nobody thought to look for this type of immune cell."

Now the team, including scientists in Canada, Germany, Sweden and Switzerland, has gone a step further, finding traces of the IgA antibody in the cerebrospinal fluid of MS patients during flare-ups, but not when episodes are in remission. They also found signs of IgA-producing immune cells in donated postmortem brain tissue that had been damaged during MS attacks. The findings confirm for the first time that gut immune cells are involved in MS relapses in humans.

"Only at the time of an attack was there an increase in these cells and the antibodies they produce," Baranzini said. "That really caught our attention."

In the hopes of determining what these gut immune cells were doing in the brain, the team then looked to see what kinds of molecules the IgA antibody reacted to. Recent research has provided evidence that an unhealthy gut microbiome plays a role in MS, when certain potentially damaging species of bacteria proliferate. While the team found that IgA did not bind to myelin protein, it did bind to some of these harmful bacteria species, suggesting that, unlike other immune cells, which are known to cause damage in MS, IgA-expressing immune cells play a protective role, possibly chasing these harmful bacteria to the brain and mounting a defense against them there.

"This opens up a whole new line of research," said Anne-Katrin Pröbstel, MD, a former UCSF postdoctoral researcher, now at the University of Basel in Switzerland and first author on the paper. "I think it has huge potential for therapeutics."

Collaborations within the UCSF Benioff Center for Microbiome Medicine allowed researchers to work with the various bacteria thought to be hallmarks of the MS microbiome, and the work relied heavily on data and biological samples collected through the multidisciplinary UCSF EPIC Study, which has followed hundreds of MS patients over 16 years.

"I think UCSF is one of the only places where we could have done this, because of the access to patient samples that allow us to look at bacteria in the gut, immune cells from the blood, immune cells from the spinal fluid and brain tissue," said Pröbstel. "It's really a unique resource."
-end-
See study online for a full list of authors, funding information, and relevant disclosures.

About UCSF: The University of California, San Francisco (UCSF) is exclusively focused on the health sciences and is dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care. It includes UCSF Health, which comprises three top-ranked hospitals, as well as affiliations throughout the Bay Area. Learn more at ucsf.edu, or see our Fact Sheet.

Follow UCSF


University of California - San Francisco

Related Multiple Sclerosis Articles from Brightsurf:

New therapy improves treatment for multiple sclerosis
A new therapy that binds a cytokine to a blood protein shows potential in treating multiple sclerosis, and may even prevent it.

'Reelin' in a new treatment for multiple sclerosis
In an animal model of multiple sclerosis (MS), decreasing the amount of a protein made in the liver significantly protected against development of the disease's characteristic symptoms and promoted recovery in symptomatic animals, UTSW scientists report.

Not all multiple sclerosis-like diseases are alike
Scientists say some myelin-damaging disorders have a distinctive pathology that groups them into a unique disease entity.

New therapeutic options for multiple sclerosis in sight
Strategies for treating multiple sclerosis have so far focused primarily on T and B cells.

Diet has an impact on the multiple sclerosis disease course
The short-chain fatty acid propionic acid influences the intestine-mediated immune regulation in people with multiple sclerosis (MS).

The gut may be involved in the development of multiple sclerosis
It is incompletely understood which factors in patients with multiple sclerosis act as a trigger for the immune system to attack the brain and spinal cord.

Slowing the progression of multiple sclerosis
Over 77,000 Canadians are living with multiple sclerosis, a disease whose causes still remain unknown.

7T MRI offers new insights into multiple sclerosis
Investigators from Brigham and Women's Hospital have completed a new study using 7 Tesla (7T) MRI -- a far more powerful imaging technology -- to further examine LME in MS patients

How to improve multiple sclerosis therapy
Medications currently used to treat multiple sclerosis (MS) can merely reduce relapses during the initial relapsing-remitting phase.

Vaccinations not a risk factor for multiple sclerosis
Data from over 12,000 multiple sclerosis (MS) patients formed the basis of a study by the Technical University of Munich (TUM) which investigated the population's vaccination behavior in relation to MS.

Read More: Multiple Sclerosis News and Multiple Sclerosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.