SerpApi.Org
B-cell depletion therapies, in which B cells of the immune system that may drive disease activity in multiple sclerosis (MS) are temporarily removed, have contributed significantly to improved treatment for patients in recent years. Researchers from the University Hospital of Bonn (UKB), the Universities of Bonn, Basel, Toronto and Yale, along with their collaborators, have uncovered a previously unknown mechanism through which B-cell depletion therapies contribute to a better disease course in patients with MS.
Subscribe to our newsletter for the latest sci-tech news updates.
Surprisingly, the treatment appears to exert part of its beneficial effect by mobilizing regulatory immune cells that naturally reside in the gut. This study has now been published in the journal Science Translational Medicine.
In multiple sclerosis (MS), the most common chronic inflammatory disease of the central nervous system, B cells, which are part of the immune system, mistakenly attack the protective sheath surrounding nerves, known as the myelin sheath. This role in the development and progression of MS has brought this type of white blood cell into focus as a therapeutic target.
It is important to note that researchers now know that not all B cells are harmful in MS. In addition to disease-causing B cells, there are also beneficial B cells that, in accordance with their actual function, help regulate immune responses and may have a positive effect on the course of the disease.
The international research team led by Professor Anne-Katrin Pröbstel from the UKB, as well as from the Universities of Basel and Bonn and the German Center for Neurodegenerative Diseases (DZNE), investigated how B-cell depletion therapies affect these protective B-cell populations.
To this end, the first authors, Dr. Tradite Neziraj and Dr. Elisabeth Pössnecker, analyzed immune cells from various tissues. They collected cells from the blood, cerebrospinal fluid and intestinal mucosal tissue of control subjects participating in the study and B-cell-depleted MS patients and examined the cells for type and function. They observed that B-cell depletion therapy promoted the trafficking of beneficial B cells from the gut into the bloodstream and central nervous system of people with MS.
Immunotherapy promotes cell migration from the gut
"Our research shows that B-cell depletion changes the levels of factors that regulate B cells and is associated with increased migration of protective gut-derived B cells," explains Pröbstel, managing director of the Center for Neurology at the University Hospital Bonn (UKB), a member of the Cluster of Excellence ImmunoSensation3 at the University of Bonn, and research group leader at the DZNE. "Interestingly, higher levels of these B cell-regulating factors were linked to better outcomes in patients with MS."
The findings provide new insights into why B-cell depletion therapies are so effective. Rather than simply removing harmful immune cells, the treatment may also help recruit beneficial immune cells from the gut. This discovery opens up new possibilities for developing future therapies that harness beneficial gut immune cells in MS and other inflammatory diseases.
More information: Tradite Neziraj et al, Anti-CD20 B cell depletion is associated with elevated mucosal-originating circulating regulatory IgA B cells in multiple sclerosis, Science Translational Medicine (2026). DOI: 10.1126/scitranslmed.aee1580. www.science.org/doi/10.1126/scitranslmed.aee1580
Provided by University Hospital of Bonn
This story was originally published on Medical Xpress.
