Targeting shared immune pathways in multiple sclerosis and type 1 diabetes: Therapeutic insights from monoclonal...

Multiple sclerosis (MS) and type 1 diabetes (T1D) are immune-mediated diseases that affect distinct target organs but display overlapping immunopathogenic mechanisms, including T- and B-cell dysregulation, common genetic susceptibility, and partially convergent environmental triggers. Epidemiological data further support a bidirectional association between the two conditions, suggesting the presence of shared autoimmune pathways. These converging features provide a rationale for exploring shared therapeutic strategies based on targeted immune modulation. Monoclonal antibodies (mAbs) have emerged as powerful tools for targeted immune modulation. In MS several mAbs, particularly B-celldepleting anti-CD20 therapies, have transformed disease management. In contrast, the therapeutic impact of immunotherapy in T1D has historically been limited by rapid and largely irreversible β-cell loss, a narrow therapeutic window, and marked disease heterogeneity. The recent approval of the anti-CD3 antibody teplizumab for delaying the onset of clinical T1D represents an important milestone in this field. This review examines shared and divergent immunological mechanisms underlying MS and T1D and evaluates monoclonal antibody therapies targeting CD3, CD20, and CD40L across both diseases. By comparing their mechanisms of action and therapeutic outcomes, we highlight how differences in molecular pathogenesis, tissue context and therapeutic window influence the effect of immunetargeted therapies. We also discuss the opportunities and limitations of cross-disease immunomodulation and emerging strategies including combination and dual-indication therapies.