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.
Neuromuscular Diseases Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA. marinos.dalakas@jefferson.edu
Marinos C
MC
Dalakas
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