Brain-specific B Cells’ Reactivity Determines Glatiramer Acetate Therapy Success in MS Patients

In a new study entitled “The brain antigen-specific B cell response correlates with glatiramer acetate responsiveness in relapsing-remitting multiple sclerosis patients,” a team of scientists discovered that differences in response to glatiramer acetate therapy among multiple sclerosis (MS) patients is potentially dependent on the presence of reactive brain-specific B cells in the patient’s blood. The study was published in the journal Scientific Reports.

MS is a chronic autoimmune disease where the patient’s own immune system attacks myelin, a component of nerve fibers that are part of the central nervous system. The disease is characterized by an initial inflammatory response that precedes demyelination and degeneration of nerve cells. MS has no cure and currently affects more than 2.3 million people in the world.

The role of B cells, a type of white blood cell and a key player in humoral immunity (antibody-mediated immunity), in the pathology of MS remains largely unaddressed.

As observed in previous findings, the researchers discovered that MS patients exhibited a brain-reactive B cell response in the blood. However, they also found that the presence of brain-specific B cells is crucial for patients’ responses to glatiramer acetate (GA) therapy in relapsing-remitting MS patients. GA is approved as a first-line immunotherapy currently used in MS, and although its mechanisms of action are unclear, it is thought to act by inhibiting the targeted immune response against myelin. This mechanism of action may occur due to its resemblance to the myelin protein, acting as a decoy to divert the autoimmune response away from myelin.

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The research team identified two subsets of MS patients, those who respond to GA therapy and those who do not. Most importantly, they discovered that MS patients harboring B cells that are responsive to brain antigens in the blood benefit the most from GA therapy.

These findings support the theory that MS exhibits a heterogeneous immunopathology, suggesting that GA therapy has an impact on brain-reactive B cells in a specific group of patients and that only this group benefits from GA treatment. These findings may lead to the development of future biomarkers that will help differentiate between treatment responders and non-responders in MS patients’ populations.