title: Complement-dependent pathogenicity of brain-specific antibodies in cerebrospinal fluid.
abstract: The specificity and potential pathogenicity of autoantibodies vary between neurological diseases. It is often unclear whether their detection in cerebrospinal fluid (CSF) is a consequence or a cause of pathology. The goal was to test whether administration of brain-specific antibodies into CSF would be sufficient for pathology. Purified immunoglobulin G from a neuromyelitis optica patient was injected intrathecally with complement to naïve mice. Histopathological analysis at 7 days revealed damage to the ependyma, disruption of the CSF parenchymal barrier and pathologic lesions, distant from the site of injection. In the absence of complement there was no pathology. Autoantibody and complement in CSF are thus sufficient to initiate a pathologic cascade.
authors.affiliation: Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, J.B. Winsloewsvej 25, DK-5000 Odense C, Denmark.
authors.forename: Nasrin
authors.initials: N
authors.lastname: Asgari
authors.forename: Reza
authors.initials: R
authors.lastname: Khorooshi
authors.forename: Søren T
authors.initials: ST
authors.lastname: Lillevang
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000276:immunology*; D001921:Brain / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D003165:Complement System Proteins / Q000134:cerebrospinal fluid* / Q000276:immunology / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D004805:Ependyma / Q000473:pathology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000134:cerebrospinal fluid* / Q000633:toxicity; D007278:Injections, Spinal; D051379:Mice; D008810:Mice, Inbred C57BL; D009471:Neuromyelitis Optica / Q000097:blood / Q000276:immunology; D014162:Transfection
chemical_list: C496030:AQP4 protein, human; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D003165:Complement System Proteins