The immune system prevents the production of antibodies that attack and damage the body’s healthy tissues.
Autoimmune diseases impair this process.
Now, research teams are examining the potential of a therapy involving B cells to fight these disorders.
Eric Meffre, a professor of medicine specializing in immunology and rheumatology at Stanford University in California and one of the researchers for the study, says the research has promising potential in treating autoimmune diseases.
“B cells are a type of white blood cell that helps fight off infections by producing antibodies, which can recognize foreign molecules and antigens, produced by pathogens, such as bacteria and viruses,” Meffre explained to Medical News Today. “Some antigens are self-antigens, which the body’s cells produce. When this occurs, the immune system recognizes them as foreign invaders and the B cells attack healthy tissue to destroy the antigens, leading to autoimmune diseases. These B cells are referred to as self-reactive.”
“The immune system works to prevent this by exposing the B cells to self-antigens as they develop in the bone marrow, called central tolerance,” he added. “Central tolerance depends on a [DNA-sensing] receptor called TLR9.”
Their findings were published today in the Journal of Experimental Medicine.
Exploring B cells and autoimmune disorders
The researchers said they discovered that depleting TLR9 stops central tolerance from occurring.
In mice, this resulted in decreased self-reactive B cells and antibodies. The researchers also reported that study participants with systemic sclerosis have decreased TLR9 activity and previous research indicated reduced activity in people with lupus.
The scientists also discovered that depleting B cells caused remission in systemic sclerosis. This autoimmune disorder damages the skin, joints, and internal organs.
“First, the scientists used rituximab to kill all B cells,” Meffre said. “The exciting news is that once the B cells are removed, all signs of the disease disappear. It was as if the disease had never existed.”
“It truly was a miracle,” he added. “The study has thus far lasted three years and there is still no sign of the disease returning, even though B cells returned in about 90 days.”
“This worked for systemic sclerosis, but not for lupus,” he noted.
“A second option is for the scientists to custom-engineer the immune system’s T-cells to attack and kill B cells,” Meffre added. “This should provide a workaround for depleting the B cells.”
However, he noted there are a few problems with this approach:
“The price tag may be worthwhile, mainly if the disease is eradicated and the process can be transferred to other autoimmune diseases instead of being customized for each person,” Meffre said. “But the research team doesn’t know how long the remission will last and if it will be long enough to make it worthwhile.”
Study provides hope for autoimmune disease treatment
Meffre said he hopes that this B-cell procedure works, that remission lasts, and that the process treats other autoimmune diseases.
“This study is elegantly conducted and offers a novel perspective on a crucial biological process: the regulation of B cell central tolerance,” said Dr. Munir Akkaya, an assistant professor at The Ohio State University College of Medicine who was not involved in the research.
“Unlike T cells, the B cell pool in our body is continually replenished by newly matured B cells while older ones are eliminated,” Akkaya explained to Medical News Today. “This ongoing process demands constant surveillance to eliminate autoreactive clones, which arise as errors in B cell development. Central and peripheral tolerance mechanisms prevent the proliferation of these potentially harmful clones by either eliminating or silencing them through various mechanisms.”
Researchers at the University of Pennsylvania are also working on eliminating some B cells as a treatment for myasthenia gravis.
This rare autoimmune disorder causes muscle weakness and trouble breathing and swallowing.
“The new approach we are developing is designed to program the patient’s immune system to kill only the autoimmune B cells that cause disease while sparing healthy B cells that can protect patients from infection,” said Dr. Aimee Payne, the director of the Penn Autoimmunity Center of Excellence, in a news release. “We are hopeful that this precision-medicine approach with CAAR T cells may if proven to be safe and effective, one day allow for a one-time infusion leading to long-term autoimmune disease remission.”
Vitamin D and autoimmune disease
Several studies in recent years have looked at the connection between vitamin D and autoimmune diseases.
A study published in 2022 found an association between vitamin D levels and autoimmunity. The researchers noted, that “it is clear that use of vitamin D to prevent autoimmune disease is possible but may require lengthy periods of supplementation.”
A 2022 study completed at Brigham and Women’s Hospital in Massachusetts looked at the effect of vitamin D with or without omega-3 fatty acids in women 55 and older, specifically whether this would lower the risk of developing an autoimmune disorder.
The researchers divided more than 25,000 women into several groups. They were randomized to receive either vitamin D with omega-3, vitamin D with a placebo, omega three with a placebo, or placebo only. They followed the participants for 5 years.
The researchers reported that supplementation with vitamin D and omega-3 fatty acids for 5 years reduced the incidence of autoimmune disease by 22% compared to no supplementation.
What’s next in autoimmune disease research
“This preclinical study offers a new mechanistic perspective on the functioning of B cell tolerance,” Akkaya said.
“The results distinctly pinpoint the TLR and CXCL4 signaling pathways as potential molecular targets, paving the way for the development of innovative therapies for individuals with autoimmune disorders,” he added. “Consequently, this marks a promising initial phase in a protracted process that could ultimately yield new pharmaceuticals.”
The timeline for clinical application, however, hinges on factors such as commercial interest and the performance of pharmacological modulators in subsequent studies focused on drug development,” Akkaya noted. “Realistically, it may take several years, and quite possibly longer, for these findings to translate into clinical utility.”
Understanding autoimmune diseases
Our bodies are constantly under attack by viruses and bacteria. Our immune system continuously works to stop these attacks and keep us healthy.
Sometimes, our immune system attacks healthy tissue, mistaking it for a threat to our health, according to the National Institutes of Health.
Some autoimmune diseases affect only one type of tissue. For example, vasculitis attacks only the blood vessels. Other conditions affect many different parts of the body. For example, lupus can damage the skin, heart, lungs, and organs.
The exact cause of autoimmune diseases isn’t well understood. However, researchers such as Meffre are working to understand why they occur and how to treat them.
There are more than 100 different autoimmune diseases. According to Mount Sinai Medical Center, some of the most common include:
Each autoimmune disease has its own set of symptoms.
Some common symptoms include:
Blood tests can usually help diagnose an autoimmune disease.
Corticosteroids help acute symptoms, according to the National Institutes of Health.
Immunosuppressants may be used for longer. These typically target specific immune system proteins. Some people may try several drugs before finding the one that works best.
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