title: Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders.
abstract: Nogo-A is a protein associated with central nervous system (CNS) myelin thought to impair regenerative responses and to suppress sprouting and plastic changes of synaptic terminals. In this study, we report that serum IgM autoantibodies to the recombinant large N-terminal inhibitory domain of Nogo-A are a frequent finding in multiple sclerosis (MS) and acute inflammatory (IND) and non-inflammatory neurological diseases (OND), but not in neurodegenerative diseases (ND), systemic inflammatory disease and healthy controls. Furthermore, we demonstrate intrathecal production of anti-Nogo-A antibodies measured by increased IgG indices. Intrathecal anti-Nogo antibodies were significantly more frequent in patients with relapsing-remitting as compared to chronic progressive (CP) MS. We also found a highly significant negative correlation of these antibody responses with age indicating that they are more frequent in younger patients. We finally demonstrate that human anti-Nogo-A antibodies recognize native Nogo-A in brain extracts, oligodendrocytes and cells expressing human Nogo-A.
authors.affiliation: Department of Neurology, University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria. markus.reindl@uibk.ac.at
authors.forename: Markus
authors.initials: M
authors.lastname: Reindl
authors.forename: Sabrina
authors.initials: S
authors.lastname: Khantane
authors.forename: Rainer
authors.initials: R
authors.lastname: Ehling
authors.forename: Kathrin
authors.initials: K
authors.lastname: Schanda
authors.forename: Andreas
authors.initials: A
authors.lastname: Lutterotti
authors.forename: Claudia
authors.initials: C
authors.lastname: Brinkhoff
authors.forename: Thomas
authors.initials: T
authors.lastname: Oertle
authors.forename: Martin E
authors.initials: ME
authors.lastname: Schwab
authors.forename: Florian
authors.initials: F
authors.lastname: Deisenhammer
authors.forename: Thomas
authors.initials: T
authors.lastname: Berger
authors.forename: Christine E
authors.initials: CE
authors.lastname: Bandtlow
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D002478:Cells, Cultured; D002493:Central Nervous System Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology; D006224:Cricetinae; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000134:cerebrospinal fluid; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000097:blood; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D009185:Myelin Proteins / Q000276:immunology*; D000070798:Nogo Proteins; D009836:Oligodendroglia / Q000276:immunology / Q000378:metabolism; D051381:Rats; D014162:Transfection
chemical_list: D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat