Invited Article: Inhibition of B cell functions
- 3 June 2008
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology
- Vol. 70 (23), 2252-2260
- https://doi.org/10.1212/01.wnl.0000313840.27060.bf
Abstract
B cells are involved in the pathophysiology of many neurologic diseases, either in a causative or contributory role, via production of autoantibodies, cytokine secretion, or by acting as antigen-presenting cells leading to T cell activation. B cells are clonally expanded in various CNS disorders, such as multiple sclerosis (MS), paraneoplastic CNS disorders, or stiff-person syndrome, and are activated to produce pathogenic autoantibodies in demyelinating neuropathies and myasthenia. B cell activating factor (BAFF) and a proliferating inducing ligand (APRIL), key cytokines for B cell survival, are strongly unregulated in MS brain and in muscles of inflammatory myopathies. Modulation of B cell functions using a series of monoclonal antibodies against CD20+ B cells or the molecules that increase B cell survival, such as BAFF/APRIL and their receptors BAFF-R, TACI, and BCMA, provide a rational approach to the treatment of the aforementioned neurologic disorders. In controlled studies, rituximab, a B cell-depleting monoclonal antibody, has been encouraging in MS and paraproteinemic anti-MAG demyelinating neuropathy, exerting long-lasting remissions. In uncontrolled series, benefit has been reported in several disorders. B cell depletion is a well-tolerated therapeutic option currently explored in the treatment of several autoimmune neurologic disorders.Keywords
This publication has 39 references indexed in Scilit:
- Targeting BAFF: Immunomodulation for autoimmune diseases and lymphomasPharmacology & Therapeutics, 2006
- A Proliferation‐inducing Ligand (APRIL) is Expressed by Astrocytes and is Increased in Multiple SclerosisScandinavian Journal of Immunology, 2006
- Rituximab: novel B-cell depletion therapy for the treatment of rheumatoid arthritisExpert Opinion on Pharmacotherapy, 2006
- Impact of the BAFF/BR3 axis on B cell survival, germinal center maintenance and antibody productionSeminars in Immunology, 2006
- An APRIL to remember: novel TNF ligands as therapeutic targetsNature Reviews Drug Discovery, 2006
- MicroRNAs hit the big timeNature Reviews Drug Discovery, 2006
- Progressive Multifocal Leukoencephalopathy Complicating Treatment with Natalizumab and Interferon Beta-1a for Multiple SclerosisNew England Journal of Medicine, 2005
- Defective B cell tolerance checkpoints in systemic lupus erythematosusThe Journal of Experimental Medicine, 2005
- Treatment of IgM antibody associated polyneuropathies using rituximabJournal of Neurology, Neurosurgery & Psychiatry, 2003
- TACI-Ig Neutralizes Molecules Critical for B Cell Development and Autoimmune DiseaseImmunity, 2001