1. Viruses and multiple sclerosis.
- Author
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Owens GP, Gilden D, Burgoon MP, Yu X, and Bennett JL
- Subjects
- Animals, B-Lymphocytes immunology, Brain immunology, Brain pathology, Central Nervous System Infections complications, Central Nervous System Infections virology, Encephalomyelitis, Autoimmune, Experimental pathology, Herpesvirus 3, Human, Herpesvirus 4, Human, Humans, Mice, Multiple Sclerosis epidemiology, Neuromyelitis Optica etiology, Neuromyelitis Optica immunology, Oligoclonal Bands cerebrospinal fluid, Peptide Library, Virus Diseases complications, Virus Diseases virology, Antigens, Viral immunology, Central Nervous System Infections immunology, Multiple Sclerosis immunology, Multiple Sclerosis virology, Virus Diseases immunology
- Abstract
Multiple sclerosis (MS) is a chronic demyelinating disorder of unknown etiology, possibly caused by a virus or virus-triggered immunopathology. The virus might reactivate after years of latency and lyse oligodendrocytes, as in progressive multifocal leukoencephalopathy, or initiate immunopathological demyelination, as in animals infected with Theiler's murine encephalomyelitis virus or coronaviruses. The argument for a viral cause of MS is supported by epidemiological analyses and studies of MS in identical twins, indicating that disease is acquired. However, the most important evidence is the presence of bands of oligoclonal IgG (OCBs) in MS brain and CSF that persist throughout the lifetime of the patient. OCBs are found almost exclusively in infectious CNS disorders, and antigenic targets of OCBs represent the agent that causes disease. Here, the authors review past attempts to identify an infectious agent in MS brain cells and discuss the promise of using recombinant antibodies generated from clonally expanded plasma cells in brain and CSF to identify disease-relevant antigens. They show how this strategy has been used successfully to analyze antigen specificity in subacute sclerosing panencephalitis, a chronic encephalitis caused by measles virus, and in neuromyelitis optica, a chronic autoimmune demyelinating disease produced by antibodies directed against the aquaporin-4 water channel.
- Published
- 2011
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