Serum and cerebrospinal fluid antibodies to Nogo-A in patients with multiple sclerosis and acute neurological disorders

• DOI: 10.1016/j.jneuroim.2003.09.010
• Publication Date: 2003-11-27T12:12:55Z
• Authors: Markus Reindl; Sabrina Khantane; Rainer Ehling; Kathrin Schanda; Andreas Lutterotti; Claudia Brinkhoff; Thomas Oertle; Martin E. Schwab; Florian Deisenhammer; Thomas Berger; Christine E. Band...
• Keywords: Adult; 0301 basic medicine; Multiple Sclerosis; Nogo Proteins; Brain; CHO Cells; Middle Aged; Autoantigens; Rats; 3. Good health; Oligodendroglia; 03 medical and health sciences; Immunoglobulin M; Central Nervous System Diseases; Cricetinae; Immunoglobulin G; Acute Disease; Animals; Humans; Cells, Cultured; Myelin Proteins; Aged; Autoantibodies

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.