B-cell depletion therapy recruits gut cells to fight MS, study suggests
Elevated signaling molecules linked to better outcomes for patients on treatment
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A 3D rendering of the microvilli architecture in the human colon. (Photo from iStock)
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B-cell depletion therapy for multiple sclerosis (MS) mobilizes protective gut-derived B-cells.
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These gut B-cells migrate to the bloodstream and nervous system, aiding treatment.
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Higher levels of two signaling proteins correlate with better outcomes in treated MS patients.
Therapies to remove harmful immune B-cells that drive inflammation in multiple sclerosis (MS) may also work by mobilizing protective, gut-derived B-cells into the bloodstream and nervous system, a new study shows.
Researchers also found that higher levels of molecules thought to drive such protective functions in B-cells were linked to better clinical outcomes in patients on B-cell-depleting treatment, pointing to a previously unrecognized mechanism behind the effectiveness of this type of therapy.
“Our research shows that B cell depletion changes the levels of factors that regulate B cells and is associated with an increased migration of protective gut-derived B cells,” Anne-Katrin Pröbstel, MD, PhD, the study’s senior author at the University of Basel in Switzerland, said in a university news story. “Interestingly, higher levels of these B cell-regulating factors were linked to better outcomes in patients with MS.”
The study, “Anti-CD20 B cell depletion is associated with elevated mucosal-originating circulating regulatory IgA B cells in multiple sclerosis,” was published in Science Translational Medicine.
Some B-cell types actually help calm immune responses
MS is a chronic inflammatory disease in which immune cells mistakenly attack the myelin sheath, the protective coating that surrounds nerve fibers. This damage disrupts communication between the brain and the body, giving rise to the disease symptoms.
Among the immune cells involved, B-cells have been identified as important drivers of disease activity. As a result, B-cell-depleting therapies, particularly those targeting the CD20 protein at the surface of most B-cells, have become a major treatment approach for MS.
While anti-CD20 therapies are known to be highly effective, scientists don’t fully understand which specific B-cell types and associated regulating factors are responsible for the clinical benefit. In fact, some B-cells types, called regulatory B-cells, actually help to calm immune responses, including the type of autoimmune responses seen in MS.
Regulatory B-cells may have migrated into brain and spinal cord
To address this gap, Pröbstel and colleagues in Switzerland, Germany, the Netherlands, Canada, and the U.S. measured gene activity and protein levels in blood, cerebrospinal fluid (CSF), and intestinal tissue samples from people with MS over time.
The CSF is the fluid surrounding the brain and spinal cord. Intestinal sampling across multiple sites was performed in one MS patient on anti-CD20 treatment and one patient not on such therapies.
The team combined patient findings with immune data from an MS animal model given an anti-CD20 treatment.
In both blood and CSF samples, the analysis showed that anti-CD20 treatment was linked to an increase in regulatory B-cells producing IgA, a type of antibody associated with mucosal tissues like the gut.
Importantly, researchers found matching genetic “fingerprints” of B-cells in both the gut and bloodstream, suggesting that these IgA-producing regulatory B-cells were migrating from the gut into the bloodstream and potentially into the brain and spinal cord.
In addition, experiments found that higher levels of two signaling proteins thought to help drive regulatory functions in B-cells — BAFF (B-cell activating factor) and APRIL (a proliferation-inducing ligand) — were associated with better clinical outcomes in people with MS undergoing anti-CD20 treatment.
These findings suggest that anti-CD20 therapy may work in part by recruiting beneficial B-cells from the gut, rather than only by removing harmful B-cells, “opening previously unknown therapeutic avenues for MS,” the researchers wrote.
Dennis
I have been diagnosed with RRMS and I take a B-12 vitamin to assist my body cope! What say You!
THOMAS ROSE
My stepfather was diagnosed in 08 i think?. He is a stubborn old carpenter with no retirement savings and he and my mom barely get by financially and cannot afford treatment. He has had no feeling from his shins down since his diagnosis. His balance has been compromised and he has managed to work through the years on scaffolding and heights in dangerous situations at times. He has taken a few falls and hurt himself a few times but nothing broken. He is tough and you cant tell him anything. He has had some new things happening this year and he has finally decided to stay on the ground level. But it feels like his ms is progressing for the first time in a while. He complains about his eye and claims to have cognitive issues. Brain fog mostly. I would love some advice. I wish i could get him on insurance and treatment. He says he cant afford the insurance and no way he and my mom can afford the treatment on their own. Thanks for reading.
Mark Collins
Thanks for the article,all of them help. Maybe one day soon you can report a vaccine for EBV. Thanks Mark
Lisa ward
I’d like to know more. Like where can one have this done
Sharon williams
This Bcell sounds good and I am wondering if it could help myself. I have hypergammaglobialanemia and told there is no cure my body is attacking me and my only option because low globulin and platelet is haemaglobulin therapy so I will need a donor for the rest of my life feeding blood into me as my Bmemry cells are very low and cannot produce antibodies if it does not work I cannot go back to antibiotic support can you help me
Fr. Glen Gleaves
Your articles are both timely and good. My MS affects my eyes -optic neuritis- so I have to use Android's Reading Mode on my S25 Ultra to read most of your long-ish articles, in order to avoid eye pain.
HOWEVER, the way you insert drug ads (like your ubiquitous Ocrevus adverts), and the way there ads are constructed, make using Reading Mode annoying! So... I avoid reading many of your articles. TRY IT YOURSELF AND SEE JUST HOW ANNOYING IT IS, having to listen to advert texts and all possible side effects that are several times longer than your article texts are.
Most of us are already on a disease-modifying drug we have chosen with our doctors, and your ads will simply go unheeded, pissing off the visually-challenged reader.