clinical topic updates
B-Cell–Depleting Therapies in Multiple Sclerosis
Overview
Current evidence suggests that B cells are involved in the pathogenesis of multiple sclerosis (MS). One piece of evidence is the persistence of oligoclonal immunoglobulins (Ig) in the cerebrospinal fluid of more than 90% of patients with MS. The oligoclonal Ig bands (OCBs) are produced as a result of intrathecal secretion of Ig by central nervous system antigen–driven B cells. Patients with MS who are positive for OCBs have been shown to have a more aggressive disease course than patients who are negative for OCBs. During their maturation, B cells express different surface molecules (eg, CD19, CD20, CD52, CD22) that distinguish the developmental stages. These surface molecules became selective targets for monoclonal antibodies, and that led to the development of B-cell–targeted therapies, including the anti-CD20 antibody ocrelizumab and the anti-CD52 antibody alemtuzumab. Recent evidence suggests that only some of the CD20-positive immune cells are pathogenic and that there are subsets of B cells that may be regulatory, potentially limiting chronic inflammation. Thus, delineating regulatory B-cell function from pathogenic B-cell properties and developing biomarkers of pathogenic B-cell function are necessary research goals that will hopefully be addressed in the near future.
Expert Commentary
David A. Hafler, MDChairman, Department of Neurology |
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“The eventual treatment of patients with MS is going to be identifying individuals genetically at risk, early diagnosis, frequent monitoring, and then treating with the goal of resetting the immune thermostat.”
The eventual treatment of patients with MS is likely to be identifying individuals genetically at risk, early diagnosis, frequent monitoring, and then treating with the goal of resetting the immune thermostat. Currently, we can deplete B cells with either alemtuzumab or ocrelizumab, but continued research may reveal that there are more specific ways of limiting the pathologic B cells, leading to the development of new therapies that could potentially reset the immune thermostat. Following treatment with a B-cell–depleting drug, we should monitor patients to determine whether they need to be re-treated. That, to me, is going to be the future of treating patients with MS . But, because neither alemtuzumab nor ocrelizumab have to be administered continuously, a woman who is planning to become pregnant could be treated beforehand and obtain the benefits of B-cell depletion, and then stop receiving treatment for an appropriate period prior to becoming pregnant and then during the pregnancy.
References
Lehmann-Horn K, Kinzel S, Weber MS. Deciphering the role of B cells in multiple sclerosis-towards specific targeting of pathogenic function. Int J Mol Sci. 2017;18(10):E2048.
Rahmanzadeh R, Weber MS, Brück W, Navardi S, Sahraian MA. B cells in multiple sclerosis therapy-a comprehensive review. Acta Neurol Scand. 2018;137(6):544-556.
Sospedra M. B cells in multiple sclerosis. Curr Opin Neurol. 2018;31(3):256-262.
