How a Multiple Sclerosis Medication Alters the Immune System Mechanisms

In 2017, ocrelizumab became the first FDA-approved therapy targeting early stages of multiple sclerosis (MS), offering hope to many patients. This monoclonal antibody works by depleting B cells—key components of the immune system involved in MS progression. However, the precise mechanisms behind its effectiveness have remained somewhat unclear. Recent research from Yale University provides new insights into how this drug influences immune cells at a cellular level.

A study published in the Journal of Clinical Investigation utilized advanced single-cell RNA sequencing to examine immune responses before and after ocrelizumab treatment in patients with early MS. Led by David A. Hafler, MD, the research revealed surprising findings: contrary to prior assumptions, the drug’s primary mode of action involves not just B cell depletion but also significant effects on other immune cells within the central nervous system.

The study found that reducing B cells led to an unexpected increase in TNF-α, a pro-inflammatory cytokine typically associated with immune activation. Paradoxically, this increase also promoted a rise in regulatory T cells, which help suppress abnormal immune responses, ultimately decreasing the attack on myelin—the protective nerve fiber sheath damaged in MS. This nuanced immune modulation explains the drug’s high efficacy.

Understanding the dynamic role of B and T cells in MS is crucial. B cells normally recognize pathogens and present them to T cells, which then orchestrate immune responses. In MS, this process becomes dysregulated, with B cells activating T cells to attack myelin, leading to neurological deficits like vision loss, weakness, and cognitive issues. Faulty regulatory T cells exacerbate this attack. Early treatment with B cell-depleting therapies like ocrelizumab can mitigate these processes before neurodegeneration advances.

Further studies analyzed the immune profiles of patients undergoing treatment, revealing that depleting B cells indirectly influences other components of the immune network, including cytokines and regulatory cells. Hafler’s team is now exploring how these insights could lead to personalized treatment strategies and a better understanding of MS’s underlying causes, such as its suspected link to Epstein-Barr virus infection.

This groundbreaking research highlights the complex biological pathways involved in MS and opens pathways for more targeted and effective therapies in the future. The findings emphasize that immune modulation can have multifaceted effects, often beyond the initial target, enriching our understanding of autoimmune diseases.

Source: https://medicalxpress.com/news/2025-07-multiple-sclerosis-drug-reshapes-immune.html