title: Autoimmune channelopathies in paraneoplastic neurological syndromes.
abstract: Paraneoplastic neurological syndromes and autoimmune encephalitides are immune neurological disorders occurring or not in association with a cancer. They are thought to be due to an autoimmune reaction against neuronal antigens ectopically expressed by the underlying tumour or by cross-reaction with an unknown infectious agent. In some instances, paraneoplastic neurological syndromes and autoimmune encephalitides are related to an antibody-induced dysfunction of ion channels, a situation that can be labelled as autoimmune channelopathies. Such functional alterations of ion channels are caused by the specific fixation of an autoantibody upon its target, implying that autoimmune channelopathies are usually highly responsive to immuno-modulatory treatments. Over the recent years, numerous autoantibodies corresponding to various neurological syndromes have been discovered and their mechanisms of action partially deciphered. Autoantibodies in neurological autoimmune channelopathies may target either directly ion channels or proteins associated to ion channels and induce channel dysfunction by various mechanisms generally leading to the reduction of synaptic expression of the considered channel. The discovery of those mechanisms of action has provided insights on the regulation of the synaptic expression of the altered channels as well as the putative roles of some of their functional subdomains. Interestingly, patients' autoantibodies themselves can be used as specific tools in order to study the functions of ion channels. This article is part of a Special Issue entitled: Membrane channels and transporters in cancers.
authors.affiliation: University Lyon 1, University Lyon, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France; INSERM, UMR-S1028, CNRS, UMR-5292, Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team, 7, Rue Guillaume Paradin, Lyon Cedex 08F-69372, France.
authors.forename: Bastien
authors.initials: B
authors.lastname: Joubert
authors.affiliation: University Lyon 1, University Lyon, Rue Guillaume Paradin, 69372 Lyon Cedex 08, France; INSERM, UMR-S1028, CNRS, UMR-5292, Lyon Neuroscience Research Center, Neuro-Oncology and Neuro-Inflammation Team, 7, Rue Guillaume Paradin, Lyon Cedex 08F-69372, France; National Reference Centre for Paraneoplastic Neurological Diseases, hospices civils de Lyon, hôpital neurologique, 69677 Bron, France; Hospices Civils de Lyon, Neuro-oncology, Hôpital Neurologique, F-69677 Bron, France. Electronic address: jerome.honnorat@chu-lyon.fr.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
mesh_terms: D001323:Autoantibodies / Q000096:biosynthesis*; D001324:Autoantigens / Q000276:immunology; D053447:Channelopathies / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D004660:Encephalitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005786:Gene Expression Regulation; D050031:Hashimoto Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020386:Isaacs Syndrome / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D020361:Paraneoplastic Syndromes, Nervous System / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018091:Receptors, AMPA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018079:Receptors, GABA / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007473:Ion Channels; D018091:Receptors, AMPA; D018079:Receptors, GABA; D016194:Receptors, N-Methyl-D-Aspartate; D011978:Receptors, Nicotinic
keywords: Lambert-Eaton myasthenic syndrome; anti-NMDAR antibodies; autoimmune channelopathies; autoimmune encephalitis; neuromyotonia; paraneoplastic neurological syndromes