Invited article: inhibition of B cell functions: implications for neurology.
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.
Dalakas
Marinos C
MC
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. marinos.dalakas@jefferson.edu
D000818:Animals; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000628:therapy; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002464:Cell Migration Inhibition / Q000276:immunology*; D006131:Growth Inhibitors / Q000494:pharmacology / Q000502:physiology*; D006801:Humans
D006131:Growth Inhibitors