title: Neuronal antigens recognized by cerebrospinal fluid IgM in multiple sclerosis.
abstract: Axonal injury is the major cause of disability in patients with multiple sclerosis (MS), but the mechanisms leading to axonal damage are poorly understood. Oligoclonal IgM against lipids predicts an aggressive disease course in MS; however, the antigen that elicits the immune response has not yet been identified. We screened the CSF of 12 patients with MS, 7 patients with neuromyelitis optica (NMO), and 5 controls with non-inflammatory neurological disease (NIND) for the presence of IgM-type antibodies (IgM-Ab) against neuronal surface antigens, and analyzed the relationship between IgM-Ab level and the extent of brain atrophy. The CSF of MS patients displayed significantly higher levels of IgM-Ab compared to NIND or NMO patients. Furthermore, we document for the first time that these IgM-Ab recognize neuronal surface antigens, and that the levels of neuronal-bound IgM-Ab were independent of the IgM concentration and correlate with brain atrophy. Our findings suggest a role for the CSF IgM-Ab in the development of MS pathophysiology.
authors.affiliation: Multiple Sclerosis Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain; Multiple Sclerosis Unit, Hospital Universitari I Politècnic La Fe, Valencia, Spain.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Beltrán
authors.forename: Alberto
authors.initials: A
authors.lastname: Hernández
authors.forename: Eva M
authors.initials: EM
authors.lastname: Lafuente
authors.forename: Francisco
authors.initials: F
authors.lastname: Coret
authors.forename: María
authors.initials: M
authors.lastname: Simó-Castelló
authors.forename: Isabel
authors.initials: I
authors.lastname: Boscá
authors.forename: Francisco Carlos
authors.initials: FC
authors.lastname: Pérez-Miralles
authors.forename: María
authors.initials: M
authors.lastname: Burgal
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Casanova
mesh_terms: D000328:Adult; D000954:Antigens, Surface / Q000378:metabolism*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology; D004586:Electrophoresis; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid; D007075:Immunoglobulin M / Q000134:cerebrospinal fluid*; D008279:Magnetic Resonance Imaging; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000134:cerebrospinal fluid* / Q000150:complications; D009422:Nervous System Diseases / Q000134:cerebrospinal fluid; D009471:Neuromyelitis Optica / Q000134:cerebrospinal fluid; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D043025:Oligoclonal Bands / Q000134:cerebrospinal fluid; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D000954:Antigens, Surface; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D043025:Oligoclonal Bands