Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders.
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.
Reindl
Markus
M
Department of Neurology, University of Innsbruck, Anichstrasse 35, Innsbruck, 6020, Austria. markus.reindl@uibk.ac.at
Khantane
Sabrina
S
Ehling
Rainer
R
Schanda
Kathrin
K
Lutterotti
Andreas
A
Brinkhoff
Claudia
C
Oertle
Thomas
T
Schwab
Martin E
ME
Deisenhammer
Florian
F
Berger
Thomas
T
Bandtlow
Christine E
CE
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
D001323:Autoantibodies; D001324:Autoantigens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D009185:Myelin Proteins; D000070798:Nogo Proteins; C000603199:RTN4 protein, human; C000603197:Rtn4 protein, rat