title: Therapeutic approaches in antibody-associated central nervous system pathologies.
abstract: Initially, antibodies targeting intracellular compounds were described in patients with paraneoplastic neurological syndromes (PNS) such as anti-Hu, anti-Yo, anti-Ri or anti-CV2/CRMP5 antibodies. As more than 90% of patients with these antibodies suffer from an associated cancer, these antibodies were used as biomarkers of an underlying tumour. Recently, autoantibodies targeting cell-surface synaptic antigens have been described in patients with neurological symptoms suggesting PNS. These autoantibodies being less frequently associated with a tumour, they completely changed the concept of PNS. They lead to a new classification, not based on clinical symptoms or oncological status but on the location of the targeted antigens. Three groups of autoantibodies can be delineated according to the neuronal localization of the targeted antigen: Group 1: cytoplasmic neuronal antigens (CNA) (anti-Hu, Yo, CV2/CRMP5, Ri, Ma1/2, Sox, Zic4). Group 2: cell-surface neuronal antigens (CSNA) (anti-NMDAR, Lgi1, CASPR2, VGCC, AMPAr, GlyR, DNER, GABABR, GABAAR, IgLONS, mGluR1 and mGluR5). Group 3: intracellular synaptic antigens (ISA) (anti-GAD65 and anti-amphiphysin). More than being solely a classification of patients, these three groups are related to profound differences in the pathophysiology and in the pathogenic role of the associated autoantibody. According to the type of associated autoantibody, the age and sex of patients, physicians are now able to predict the presence or absence of tumour, the clinical evolution and prognostic and also the response to immunomodulator treatments that differ fundamentally from one group to the others.
authors.affiliation: Neuro-oncologie, French Reference Center on Paraneoplastic Neurological Syndrome, hôpital neurologique Pierre-Wertheimer, hospices civils de Lyon, 59, boulevard Pinel, 69677 Bron cedex, France; Lyon Neuroscience Research Center, Inserm U1028/CNRS UMR 5292, faculté Laennec, 9, rue Guillaume-Paradin, 69003 Lyon, France; Université de Lyon, université Claude-Bernard Lyon 1, 43, boulevard du 11 novembre 1918, 69100 Villeurbanne, France. Electronic address: jerome.honnorat@chu-lyon.fr.
authors.forename: J
authors.initials: J
authors.lastname: Honnorat
mesh_terms: D000954:Antigens, Surface / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D002493:Central Nervous System Diseases / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D009474:Neurons / Q000276:immunology
chemical_list: D000954:Antigens, Surface; D001323:Autoantibodies
keywords: Antigènes neuronaux membranaires; Auto-anticorps; Autoantibodies; Autoimmune encephalitides; Encéphalites auto-immunes; Immunisation; Immunomodulation; NMDA receptor; Paraneoplastic neurological syndromes; Récepteur NMDA; Synaptic antigens; Syndromes neurologiques paranéoplasiques