B-cell depletion therapies, which temporarily remove B cells from the immune system, have led to improved outcomes for patients with multiple sclerosis, according to a study published on Jul. 22 in Science Translational Medicine. An international research team from the University Hospital of Bonn, the Universities of Bonn, Basel, Toronto, and Yale found that these therapies may work in part by mobilizing regulatory immune cells naturally residing in the gut.
Multiple sclerosis is a chronic inflammatory disease where B cells mistakenly attack the myelin sheath surrounding nerves. While some B cells contribute to disease progression, others help regulate immune responses and may positively affect disease course. The study investigated how B-cell depletion therapies impact both harmful and beneficial B cell populations.
Dr. Tradite Neziraj and Dr. Elisabeth Pössnecker analyzed immune cells collected from blood, cerebrospinal fluid, and intestinal mucosal tissue of control subjects and MS patients who had undergone B-cell depletion therapy. They observed that this therapy promoted the movement of beneficial gut-derived B cells into the bloodstream and central nervous system.
"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," said Prof. Dr. Anne-Katrin Pröbstel, Managing Director of the Center for Neurology at University Hospital Bonn (UKB). "Interestingly, higher levels of these B cell-regulating factors were linked to better outcomes in patients with MS."
The findings suggest that rather than simply removing harmful immune cells, these treatments may also recruit beneficial ones from the gut. The discovery could inform future therapeutic strategies for MS or other inflammatory diseases by targeting or harnessing protective gut-derived immune cells.
The study was conducted with collaborators from Université de Lausanne and UMC Amsterdam and received funding from organizations including the Swiss Multiple Sclerosis Society (SMSG), Propatient Stiftung at University Hospital Basel, Fondation Pierre Mercier pour la Science, National Multiple Sclerosis Society, Swiss National Science Foundation (SNF), State Secretariat for Education Research and Innovation under Horizon 2020 program grant, German Research Foundation as part of Germany's Excellence Strategy; Dr. Neziraj also received support through an Early Investigator Research Award from the U.S. Department of Defense's Multiple Sclerosis Research Program.
