[Plasmablast in the pathology of multiple sclerosis]

Area of Science:

• Neuroimmunology
• Autoimmune diseases of the central nervous system

Context:

• Multiple sclerosis (MS) is a heterogeneous autoimmune disorder affecting the central nervous system.
• A significant portion of MS patients do not respond to first-line interferon-beta (IFN-β) therapy, with underlying reasons unclear.
• Neuromyelitis optica (NMO), an MS-like disease, is resistant to IFN-β and characterized by B cells producing autoantibodies against aquaporin 4 (AQP4).

Purpose:

• To investigate if B-cell abnormalities, similar to those in NMO, contribute to IFN-β non-responsiveness in MS.
• To identify potential biomarkers and therapeutic targets for non-responsive MS patients.

Summary:

• Researchers identified an expansion of circulating plasma B cells (PBs) in MS patients unresponsive to IFN-β.
• These PBs demonstrated IL-6-dependent survival in vitro, mirroring mechanisms observed in NMO.
• Clinical characteristics of these 'PB-high' patients correlated with autoantibody-mediated pathology.

Impact:

• This study reveals a potential mechanism for IFN-β non-responsiveness in MS, linked to IL-6-dependent B cells.
• It supports the use of tocilizumab, an anti-IL-6 receptor antibody, for precision medicine in intractable MS cases.
• Findings pave the way for targeted therapies in specific MS patient subgroups.