• Protective effect
• Helper cells
What is already known about this topic
Multiple sclerosis is an autoimmune disease in which immune cells attack neurons’ protective covers, leading to muscle weakness, blindness, and even death. Although previous studies have identified particular bacteria present in increased amounts in the guts of people with multiple sclerosis, little is known about the causes of the disease.What this research adds
By looking at particular gut antibodies in the cerebrospinal fluid from people with multiple sclerosis, researchers found high levels of particular gut antibodies in the central nervous systems of people with multiple sclerosis flare-ups. These antibodies also react to certain species of gut microbes, suggesting that specific immune cells that originate in the gut can traffic to the central nervous system, where they contribute to bring flare-ups under control.Conclusion
The findings could pave the way for new diagnostic approaches and treatments for multiple sclerosis that target the intestinal flora.
Multiple sclerosis affects 2.5 million people worldwide, but little is known about what causes the disease, which can lead to muscle weakness, blindness, and even death. Now, researchers have found that people with active multiple sclerosis have high levels of particular gut antibodies in the central nervous systems. These antibodies also react to certain species of gut microbes, suggesting that specific immune cells that originate in the gut can traffic to the central nervous system, where they contribute to bring flare-ups under control.
The findings, published in Science Immunology, could pave the way for new diagnostic approaches and treatments for multiple sclerosis that target the intestinal flora.
Multiple sclerosis is an autoimmune disease in which immune cells attack neurons’ protective covers, disrupting the information flow from and within the brain. Previous research found a specific kind of antibody, called immunoglobulin A (IgA), in fecal samples from people and mice with multiple sclerosis that suffered active neuroinflammation.
To further elucidate the link between IgA and multiple sclerosis, researchers led by Anne-Katrin Pröbstel at the University of Basel and Sergio Baranzini at the University of California, San Francisco, studied IgA levels in fecal, blood, and cerebrospinal fluid samples from people with multiple sclerosis, and compared them with samples from individuals with neurodegenerative disease as well as healthy controls.
Protective effect
The researchers found that, compared to people with neurodegenerative disease and healthy controls, individuals with multiple sclerosis had higher levels of IgA antibodies and a high frequency of IgA-producing immune cells in their spinal fluid.
Traces of IgA antibodies were found only in the cerebrospinal fluid of multiple sclerosis patients during flare-ups, but not when episodes were in remission. “Only at the time of an attack was there an increase in these cells and the antibodies they produce,” Baranzini says. “That really caught our attention.”
What’s more, in postmortem brain samples from people with multiple sclerosis, the team identified an enrichment of IgA-producing immune cells in areas near the nerves damaged by multiple sclerosis.
Helper cells
In further experiments, the researchers analyzed the role of IgA-producing immune cells in the central nervous systems of 56 individuals with multiple sclerosis during acute flare-ups. IgA antibodies reacted to certain species of gut microbes, suggesting the intestinal origins of some IgA-producing immune cells.
The team hypothesized that these gut immune cells could migrate to the central nervous system, where they contribute to bring flare-ups under control. “That could explain why the illness worsens if these immune cells are removed from the blood with medication,” Pröbstel says.
What activates IgA-producing immune cells and prompts their migration from the gut to the central nervous system is still unclear. “If we find the trigger for that, we could use it to treat multiple sclerosis,” Pröbstel says. For example, microbiota-based treatments for multiple sclerosis could change the composition of the intestinal flora of patients to stimulate the protective function of IgA-producing immune cells during flare-ups, the researchers say.
